bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Pathways: Targeting Hsp90—Who Benefits and Who Does Not
Authors: Scaltriti Maurizio , Dawood Shaheenah , Cortes Javier
Published: June 2012

Many kinases and hormone receptors, important for cancer cell proliferation and survival, bind to and are dependent on the Hsp90 cycle for their folding and maturation. This provides the rationale for the development of small-molecule ATP competitors that, inhibiting Hsp90 function, lead to degradation of the "client" proteins. After continual efforts to improve the pharmacologic properties and the tolerability of these molecules, several Hsp90 inhibitors have exhibited activity in both preclinical models and in the clinical setting. As is the case with many other targeted agents, patient selection seems to be the major limitation to the success of these compounds. ERBB2-positive patients with breast cancer are exquisitely sensitive to Hsp90 inhibition. This is because ERBB2 is indispensable for growth and survival of this subtype of cancer, and at the same time ERBB2 is a client protein strictly dependent on Hsp90 for its maturation and stability. Extensive preclinical work identifying other ERBB-like client proteins will likely lead to the ability to enhance selection of appropriate patients for enrollment in more rational clinical trials. Hsp90 inhibition has also been reported to synergize with other therapeutic agents. Several ongoing studies testing different combinations of Hsp90 inhibitors with other targeted agents will confirm whether Hsp90 inhibition can potentiate the efficacy of targeted therapy and/or prevent the emergence of drug resistance. Clin Cancer Res; 18(17); 4508–13. ©2012 AACR.
Regulatory Polymorphisms in β-Tubulin IIa Are Associated with Paclitaxel-Induced Peripheral Neuropathy
Authors: Leandro-García Luis J. , Leskelä Susanna , Jara Carlos , Gréen Henrik , Åvall-Lundqvist Elisabeth , Wheeler Heather E. , Dolan M. Eileen , Inglada-Perez Lucia , Maliszewska Agnieszka , de Cubas Aguirre A. , Comino-Méndez Iñaki , Mancikova Veronika , Cascón Alberto , Robledo Mercedes , Rodríguez-Antona Cristina
Published: June 2012

Purpose: Peripheral neuropathy is the dose-limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat several solid tumors such as breast, lung, and ovary. The cytotoxic effect of paclitaxel is mediated through β-tubulin binding in the cellular microtubules. In this study, we investigated the association between paclitaxel neurotoxicity risk and regulatory genetic variants in β-tubulin genes.

Experimental Design: We measured variation in gene expression of three β-tubulin isotypes (I, IVb, and IIa) in lymphocytes from 100 healthy volunteers, sequenced the promoter region to identify polymorphisms putatively influencing gene expression and assessed the transcription rate of the identified variants using luciferase assays. To determine whether the identified regulatory polymorphisms were associated with paclitaxel neurotoxicity, we genotyped them in 214 patients treated with paclitaxel. In addition, paclitaxel-induced cytotoxicity in lymphoblastoid cell lines was compared with β-tubulin expression as measured by Affymetrix exon array.

Results: We found a 63-fold variation in β-tubulin IIa gene (TUBB2A) mRNA content and three polymorphisms located at −101, −112, and −157 in TUBB2A promoter correlated with increased mRNA levels. The −101 and −112 variants, in total linkage disequilibrium, conferred TUBB2A increased transcription rate. Furthermore, these variants protected from paclitaxel-induced peripheral neuropathy [HR, 0.62; 95% confidence interval (CI), 0.42–0.93; P = 0.021, multivariable analysis]. In addition, an inverse correlation between TUBB2A and paclitaxel-induced apoptosis (P = 0.001) in lymphoblastoid cell lines further supported that higher TUBB2A gene expression conferred lower paclitaxel sensitivity.

Conclusions: This is the first study showing that paclitaxel neuropathy risk is influenced by polymorphisms regulating the expression of a β-tubulin gene. Clin Cancer Res; 18(16); 4441–8. ©2012 AACR.
Molecular Profiling of Patients with Colorectal Cancer and Matched Targeted Therapy in Phase I Clinical Trials
Authors: Dienstmann Rodrigo , Serpico Danila , Rodon Jordi , Saura Cristina , Macarulla Teresa , Elez Elena , Alsina Maria , Capdevila Jaume , Perez-Garcia Jose , Sánchez-Ollé Gessamí , Aura Claudia , Prudkin Ludmila , Landolfi Stefania , Hernández-Losa Javier , Vivancos Ana , Tabernero Josep
Published: June 2012

Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients with cancer. In keeping with the exigencies of a personalized oncology program, tumors from patients with advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN and pMET expression). Patients were subsequently offered phase I trials with matched targeted agents (MTA) directed at the identified anomalies. During 2010 and 2011, tumor molecular analysis was conducted in 254 patients: KRAS mutations (80 of 254, 31.5%), BRAF mutations (24 of 196, 12.2%), PIK3CA mutations (15 of 114, 13.2%), KRAS and PIK3CA mutations (9 of 114, 7.9%), low PTEN expression (97 of 183, 53.0%), and high pMET expression (38 of 64, 59.4%). In total, 68 patients received 82 different MTAs: phosphoinositide 3-kinase (PI3K) pathway inhibitor (if PIK3CA mutation, n = 10; or low PTEN, n = 32), PI3K pathway inhibitor plus MEK inhibitor (if KRAS mutation, n = 10; or BRAF mutation, n = 1), second-generation anti-EGF receptor monoclonal antibodies (if wild-type KRAS, n = 11), anti-hepatocyte growth factor monoclonal antibody (if high pMET, n = 10), mTOR inhibitor plus anti-insulin-like growth factor-1 receptor monoclonal antibody (if low PTEN, n = 5), and BRAF inhibitor (if BRAF mutation, n = 3). Median time-to-treatment failure on MTA was 7.9 versus 16.3 weeks for their prior systemic antitumor therapy (P < 0.001). Partial response was seen in 1 patient [1.2%, PI3K inhibitor with PIK3CA mutation] and stable disease >16 weeks in 10 cases (12.2%). These results suggest that matching chemorefractory patients with colorectal cancer with targeted agents in phase I trials based on the current molecular profile does not confer a significant clinical benefit. Mol Cancer Ther; 11(9); 2062–71. ©2012 AACR.
Obesity and Metabolic Syndrome: An Inflammatory Condition
Authors: Scarpellini E. , Tack J.
Published: June 2012

Obesity causes chronic low-grade inflammation that contributes to systemic metabolic dysfunction associated with obesity-linked disorders that fall under the definition of metabolic syndrome. Adipose tissue is a key endocrine organ as it releases multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have proinflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this emerging context, the gut microbiota-metabolism interactions play an increasingly important role in the understanding and hopefully future treatment of complex metabolic unbalances responsible for insulin resistance and cardiovascular high-risk diseases.
Association of the –1072G/A Polymorphism in the LTC4S Gene with Asthma in an Indian Population
Authors: Kumar Amrendra , Sharma Shilpy , Agrawal Anurag , Ghosh Balaram
Published: June 2012

Background: Atopic asthma, the most common chronic disease affecting children and young adults, is a complex disorder with variable phenotypes. Cysteine leukotrienes (Cys-LTs) are powerful bronchoconstrictors and play a critical role in airway inflammation and remodeling that are characteristic of asthma. Objective: To investigate the association of ALOX5, LTC4S and CysLTR2 gene polymorphisms with atopic asthma in an Indian population. Methods: A total of 19 single nucleotide polymorphisms (SNPs) within these genes were genotyped in a family-based cohort (n = 239) and a case-control cohort (139 cases and 194 controls) followed by association analyses. Results: We found a significant association of the –1072G/A (rs3776944) SNP with atopic asthma in the family-based association analysis (p = 0.0004). These results were also replicated in the case-control cohort (p = 0.009). The allele A was negatively associated with atopic asthma. We also noted a significant association in the two-locus (rs3776944G/A and rs730012A/C) haplotypic analysis of this gene both in the family-based (p = 0.03) and the case-control (p = 0.02) analyses. Conclusion: This study supports the role of the LTC4S gene polymorphism in genetic susceptibility to atopic asthma in an Indian population.
Pharmacokinetic Study of S-1 in Patients in Whom Inulin Clearance Was Measured
Authors: Ando Yuichi , Kawada Kenji , Inada Megumi , Morita Sachi , Mitsuma Ayako , Yasuda Yoshinari , Hiramatsu Mariko , Fujimoto Yasushi , Fujita Ken-ichi
Published: June 2012

Objective: This pharmacokinetic study of S-1 was conducted in patients in whom glomerular filtration rate (GFR) was directly measured to explore the possibility of adjusting the S-1 dose on the basis of GFR in patients with normal or nearly normal renal function. Methods: S-1 was given to 12 patients twice daily for 28 consecutive days followed by 14 days of rest, repeated every 6 weeks. GFR was measured on the basis of inulin clearance (CLin) before the first day of treatment. Results: The area under the time-concentration curve (AUC) of 5-fluorouracil (5-FU) correlated with that of 5-chloro-2,4-dihydroxypyridine (CDHP, r = 0.750, p = 0.005). The AUC of CDHP correlated with the measured 24-hour creatinine clearance (CLcr) per subject (r = –0.620, p = 0.032), but not with the CLin (r = –0.356, p = 0.257). The AUC of 5-FU did not correlate with either the 24-hour CLcr per subject (r = –0.401, p = 0.187) or with the CLin (r = –0.300, p = 0.351). Conclusion: Dosage adjustment based on the GFR does not reduce individual variations in 5-FU concentrations among patients with normal or nearly normal renal function who receive S-1.
Role of Reactive Oxygen Species in Transforming Growth Factor Beta1-Induced Alpha Smooth-Muscle Actin and Collagen Production in Nasal Polyp-Derived Fibroblasts
Authors: Park Il-Ho , Park Se-Jin , Cho Jung-Sun , Moon You-Mi , Kim Tae Hoon , Lee Sang Hag , Lee Heung-Man
Published: June 2012

Background: Myofibroblasts are detected in nasal polyps and are involved in nasal polyp formation by inducing extracellular matrix accumulation. Reactive oxygen species (ROS) are released during the differentiation of fibroblasts to myofibroblasts. The purpose of this study was to investigate ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) expression in nasal polyp-derived fibroblasts (NPDFs) and to evaluate whether ROS from NOX mediates transforming growth factor (TGF)-β1-induced production of alpha smooth-muscle actin (α-SMA) and collagen production. Methods: NPDFs were incubated and treated with TGF-β1. The mRNA expression of NOXs, α-SMA, and collagen type I and IV was determined by reverse transcription-polymerase chain reaction, and the expression of α-SMA protein was determined by immunofluorescence microscopy. The amount of total soluble collagen production was analyzed by the SirCol assay. The ROS generation of cells was investigated using the 2′,7′-dichlorfluorescein-diacetate. The fluorescence was captured by fluorescent microscope and measured using a fluorometer. Results: Stimulation with TGF-β1 increased ROS production by NPDFs compared with NPDFs not treated with TGF-β1. Stimulation with TGF-β1 increased the expression of NOX4 mRNA most potently among various Nox enzymes. siNOX4 was able to decrease the level of ROS production. Myofibroblast differentiation and the production of collagen in NPDFs were prevented by inhibition of ROS generation with diphenyliodonium, N-acetylcysteine, ebselen, and siNox4. Conclusions: This study showed that NOX4 and ROS have a role in myofibroblast differentiation and collagen production of TGF-β1-induced NPDFs and that these processes are inhibited by the elimination of ROS.
Postoperative Depot Medroxyprogesterone Acetate versus Continuous Oral Contraceptive Pills in the Treatment of Endometriosis-Associated Pain: A Randomized Comparative Trial
Authors: Cheewadhanaraks Sopon , Choksuchat Chainarong , Dhanaworavibul Kriengsak , Liabsuetrakul Tippawan
Published: June 2012

Background/Aim: To evaluate the efficacy and tolerability of postoperative depot medroxyprogesterone acetate (DMPA) versus postoperative continuous oral contraceptive (OC) pills in the treatment of endometriosis-associated pain. Methods: After a conservative surgery, 84 patients with symptomatic endometriosis were randomized to receive either intramuscular DMPA (150 mg) every 12 weeks for 24 weeks or continuous OC pills (ethinyl estradiol 0.03 mg and gestodene 0.075 mg) daily for 24 weeks. At weeks 12 and 24 of the treatment phase, patients rated their satisfaction with treatment and reported pain improvement and adverse effects. Results: There was no significant difference in the percentages of patients who reported satisfaction between the DMPA group and the OC group at weeks 12 and 24 (92.9 vs. 90.5%, and 92.9 vs. 88.1%, respectively). The rates of withdrawal because of persistent pain or side effects in the two groups were similar. Pain scores improved significantly in both groups, but dysmenorrhea scores on a visual analog scale at week 24 were significantly higher in the OC group than in the DMPA group (p = 0.039). Conclusion: Both postoperative DMPA and postoperative OC pills for 24 weeks were found to be effective and acceptable options for treating endometriosis-associated pain.
Palaeopathology of Human Remains from the Roman Imperial Age
Authors: Minozzi Simona , Catalano Paola , Caldarini Carla , Fornaciari Gino
Published: June 2012

The increasing attention of archaeological and anthropological research towards palaeopathological studies has allowed to focus the examination of many skeletal samples on this aspect and to evaluate the presence of many diseases afflicting ancient populations. This paper describes the most interesting diseases observed in skeletal samples from five necropolises found in urban and suburban areas of Rome during archaeological excavations in the last decades, and dating back to the Imperial Age. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumors, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, palaeopathology allowed highlighting the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.
Congenital Idiopathic Dilatation of the Right Atrium: Antenatal Appearance, Postnatal Management, Long-Term Follow-Up and Possible Pathomechanism
Authors: Hofmann Sigrun R. , Heilmann Antje , Häusler Hans J. , Dähnert Ingo , Kamin Gabriele , Lachmann Robert
Published: June 2012

Introduction: Idiopathic dilatation of the right atrium (IDRA) is a rare abnormality usually detected by chance at any time between antenatal and adult life. It is defined as isolated enlargement of the right atrium in the absence of other cardiac lesions causing right atrial dilatation. IDRA can be associated with atrial arrhythmia and systemic embolism. The clinical presentation shows high variability ranging from the lack of any symptoms up to cardiac failure. Methods/Results: We describe 2 children with antenatally diagnosed IDRA, the intrauterine course in 1 case, the postnatal management and its long-term follow-up. There has been no need for surgical intervention so far because of the lack of arrhythmias and no further progression of right atrial diameters. Thrombus formation in the right atrium, which is a potential risk for pulmonary embolism, led us to initiate anticoagulation in our cases to prevent such complications. Furthermore, we suggest one possible pathomechanism of congenital right atrial dilatation. Conclusion: Optimal management of severe IDRA depends on the individual case. Long-term follow-up of these patients is necessary to monitor a possible further progression of right atrial size and occurrence of arrhythmias. As a possible pathomechanism, a functional partial anomalous pulmonary venous insertion may imitate a structural abnormal pulmonary vein connection in some idiopathic cases of congenital right atrial dilatation.
Learning to Sample: Eye Tracking and fMRI Indices of Changes in Object Perception
Authors: Emberson Lauren L. , Amso Dima
Published: June 2012

We used an fMRI/eye-tracking approach to examine the mechanisms involved in learning to segment a novel, occluded object in a scene. Previous research has suggested a role for effective visual sampling and prior experience in the development of mature object perception. However, it remains unclear how the naive system integrates across variable sampled experiences to induce perceptual change. We generated a Target Scene in which a novel occluded Target Object could be perceived as either “disconnected” or “complete.” We presented one group of participants with this scene in alternating sequence with variable visual experience: three Paired Scenes consisting of the same Target Object in variable rotations and states of occlusion. A second control group was presented with similar Paired Scenes that did not incorporate the Target Object. We found that, relative to the Control condition, participants in the Training condition were significantly more likely to change their percept from “disconnected” to “connected,” as indexed by pretraining and posttraining test performance. In addition, gaze patterns during Target Scene inspection differed as a function of variable object exposure. We found increased looking to the Target Object in the Training compared with the Control condition. This pattern was not restricted to participants who changed their initial “disconnected” object percept. Neuroimaging data suggest an involvement of the hippocampus and BG, as well as visual cortical and fronto-parietal regions, in using ongoing regular experience to enable changes in amodal completion.
BOLD Responses to Tactile Stimuli in Visual and Auditory Cortex Depend on the Frequency Content of Stimulation
Authors: Nordmark Per F. , Pruszynski J. Andrew , Johansson Roland S.
Published: June 2012

Although some brain areas preferentially process information from a particular sensory modality, these areas can also respond to other modalities. Here we used fMRI to show that such responsiveness to tactile stimuli depends on the temporal frequency of stimulation. Participants performed a tactile threshold-tracking task where the tip of either their left or right middle finger was stimulated at 3, 20, or 100 Hz. Whole-brain analysis revealed an effect of stimulus frequency in two regions: the auditory cortex and the visual cortex. The BOLD response in the auditory cortex was stronger during stimulation at hearable frequencies (20 and 100 Hz) whereas the response in the visual cortex was suppressed at infrasonic frequencies (3 Hz). Regardless of which hand was stimulated, the frequency-dependent effects were lateralized to the left auditory cortex and the right visual cortex. Furthermore, the frequency-dependent effects in both areas were abolished when the participants performed a visual task while receiving identical tactile stimulation as in the tactile threshold-tracking task. We interpret these findings in the context of the metamodal theory of brain function, which posits that brain areas contribute to sensory processing by performing specific computations regardless of input modality.
Context-dependent Changes in Functional Connectivity of Auditory Cortices during the Perception of Object Words
Authors: van Dam Wessel O. , van Dongen Eelco V. , Bekkering Harold , Rueschemeyer Shirley-Ann
Published: June 2012

Embodied theories hold that cognitive concepts are grounded in our sensorimotor systems. Specifically, a number of behavioral and neuroimaging studies have buttressed the idea that language concepts are represented in areas involved in perception and action [Pulvermueller, F. Brain mechanisms linking language and action. Nature Reviews Neuroscience, 6, 576–582, 2005; Barsalou, L. W. Perceptual symbol systems. Behavioral and Brain Sciences, 22, 577–660, 1999]. Proponents of a strong embodied account argue that activity in perception/action areas is triggered automatically upon encountering a word and reflect static semantic representations. In contrast to what would be expected if lexical semantic representations are automatically triggered upon encountering a word, a number of studies failed to find motor-related activity for words with a putative action-semantic component [Raposo, A., Moss, H. E., Stamatakis, E. A., & Tyler, L. K. Modulation of motor and premotor cortices by actions, action words and action sentences. Neuropsychologia, 47, 388–396, 2009; Rueschemeyer, S.-A., Brass, M., & Friederici, A. D. Comprehending prehending: Neural correlates of processing verbs with motor stems. Journal of Cognitive Neuroscience, 19, 855–865, 2007]. In a recent fMRI study, Van Dam and colleagues [Van Dam, W. O., Van Dijk, M., Bekkering, H., & Rueschemeyer, S.-A. Flexibility in embodied lexical-semantic representations. Human Brain Mapping, in press] showed that the degree to which a modality-specific region contributes to a representation considerably changes as a function of context. In the current study, we presented words for which both motor and visual properties (e.g., tennis ball, boxing glove) were important in constituting the concept. Our aim was to corroborate on earlier findings of flexible and context-dependent language representations by testing whether functional integration between auditory brain regions and perception/action areas is modulated by context. Functional connectivity was investigated by means of a psychophysiological interaction analysis, in which we found that bilateral superior temporal gyrus was more strongly connected with brain regions relevant for coding action information: (1) for Action Color words vs. Abstract words, and (2) for Action Color words presented in a context that emphasized action vs. a context that emphasized color properties.
Impaired Conflict Adaptation in an Emotional Task Context following Rostral Anterior Cingulate Cortex Lesions in Humans
Authors: Maier Martin E. , di Pellegrino Giuseppe
Published: June 2012

Recent brain imaging studies have implicated the rostral ACC (rACC) in the resolution of conflict between competing response tendencies in emotional task contexts, but not in neutral task contexts. This study tested the hypothesis that the rACC is necessary for such context-specific conflict adaptation. To this end, a group of patients with lesions of the rACC, a group of brain-damaged controls, and a group of normal controls classified the emotional expression (emotional task context) or the gender (neutral task context) of faces while ignoring congruent and incongruent words written across the faces. In all three groups, performance was worse with incongruent as compared with congruent stimuli in both task contexts. In the two control groups, this congruency effect was reduced following incongruent trials in both task contexts. By contrast, the rACC group displayed such conflict adaptation only in the neutral, but not in the emotional, task context. These results show that the rACC is necessary for conflict adaptation in emotional but not in neutral task contexts and suggest that the regulation of behavior is context specific.
Evaluating Data Assimilation Algorithms
Authors: Law K. J. H. , Stuart A. M.
Published: June 2012

Data assimilation leads naturally to a Bayesian formulation in which the posterior probability distribution of the system state, given all the observations on a time window of interest, plays a central conceptual role. The aim of this paper is to use this Bayesian posterior probability distribution as a gold standard against which to evaluate various commonly used data assimilation algorithms.

A key aspect of geophysical data assimilation is the high dimensionality and limited predictability of the computational model. This paper examines the two-dimensional Navier–Stokes equations in a periodic geometry, which has these features and yet is tractable for explicit and accurate computation of the posterior distribution by state-of-the-art statistical sampling techniques. The commonly used algorithms that are evaluated, as quantified by the relative error in reproducing moments of the posterior, are four-dimensional variational data assimilation (4DVAR) and a variety of sequential filtering approximations based on three-dimensional variational data assimilation (3DVAR) and on extended and ensemble Kalman filters.

The primary conclusions are that, under the assumption of a well-defined posterior probability distribution, (i) with appropriate parameter choices, approximate filters can perform well in reproducing the mean of the desired probability distribution, (ii) they do not perform as well in reproducing the covariance, and (iii) the error is compounded by the need to modify the covariance, in order to induce stability. Thus, filters can be a useful tool in predicting mean behavior but should be viewed with caution as predictors of uncertainty. These conclusions are intrinsic to the algorithms when assumptions underlying them are not valid and will not change if the model complexity is increased.
‘Earning and learning’ in those with psychotic disorders: The second Australian national survey of psychosis
Authors: Waghorn Geoffrey , Saha Sukanta , Harvey Carol , Morgan Vera A , Waterreus Anna , Bush Robert , Castle David , Galletly Cherrie , Stain Helen J , Neil Amanda L , McGorry Patrick , McGrath John J
Published: June 2012

Objective:

Participation in mainstream education and employment facilitates both the recovery and the social inclusion of people with psychotic disorders. As part of the second Australian survey of psychosis, we assessed labour force activity and participation in formal education among working age adults with psychotic disorders.

Method:

Data were drawn from a large national community prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas during March to December 2010. Current and past year labour force activity, current employment, past year participation in formal education and vocational training, and key clinical and demographic characteristics were examined in a sample of 1825 participants.

Results:

Only 22.4% of people with psychotic disorders were found to be employed (either full-time or part-time) in the month prior to the survey. In the previous 12 months, 32.7% were employed at some time. Of those in competitive employment, the majority worked part-time (63.9%), while a quarter worked 38 or more hours per week (23.4%). In terms of educational attainment, 18.4% reported difficulties with reading or writing, while 31.9% completed high school, which represents 12 years of formal education.

Conclusions:

The proportion currently employed has remained stable at 22% since the last national survey in 1997. Policy makers and service providers could do more to ensure people with psychotic disorders obtain access to more effective forms of assistance with respect to both their continuing education and employment. More effective vocational and educational interventions for people with psychotic disorders appear to be urgently needed.
Disentangling the ‘New Liberal Dilemma’: On the relation between general welfare redistribution preferences and welfare chauvinism
Authors: Reeskens Tim , van Oorschot Wim
Published: June 2012

In the present ‘Age of Migration’, public policy as well as social scientists are puzzled by the ‘New Liberal Dilemma’ (Newton, 2007) of finding popular support for welfare programs that have been installed in times of cultural homogeneity. In this article, we are interested in the question of whether opinions about immigrants’ access to welfare provisions originate from general preferences towards welfare redistribution, and whether this association is moderated by the national context. Using the 2008 wave of the European Social Survey, we show that particularly those who favor that welfare benefits should in the first place target the neediest, place the highest restrictions on welfare provisions for immigrants. In addition, the relationship between preferences for welfare redistribution and opinions about immigrants’ access to social welfare is moderated by a national context of cultural heterogeneity. We conclude the article by drawing implications for public policy.
The Relationship Between Life Satisfaction and Emotional Experience in 21 European Countries
Authors: Kööts-Ausmees Liisi , Realo Anu , Allik Jüri
Published: June 2012

In the current study, the relationship between life satisfaction (LS) and the affective components of subjective well-being (SWB) was examined in a sample of 40,487 people across 21 European countries using data from the European Social Survey. After running multilevel confirmatory factor analyses in order to establish the measurement invariance of the constructs across the countries, the individual-level dataset was linked to available country-level aggregate personality traits, cultural values, and human development index (HDI). Results from hierarchical linear modeling (HLM) analysis showed that LS is best predicted by positive and negative affect (PA and NA, respectively), but may also be predicted by the degree of mixed emotions (ME). At the country level, national mean scores of Extraversion and Neuroticism moderated the relationship between LS and ME in different directions, whereas neither of the two personality traits had a significant impact on the relationship of LS to PA and NA. Survival/self-expression and the HDI ranking influenced the LS-PA and LS-ME relationships, whereas individualism/collectivism did not. Our research indicates that in addition to analyzing separate effects of NA and PA, it is also important to consider emotional complexity in SWB research, whereas these analyses need to take into account the moderating effect of cultural aspects, such as survival/self-expression values and countries’ level of development. Our findings also emphasize the importance of employing representative samples, as the age variance of participants can have a profound impact on results.
The Benefits of a Friendship-Based HIV/STI Prevention Intervention for African American Youth
Authors: Harper Gary W. , Dolcini M. Margaret , Benhorin Shira , Watson Susan E. , Boyer Cherrie B.
Published: June 2012

This article presents findings from a qualitative evaluation of an HIV/STI (sexually transmitted infection) prevention intervention for urban African American youth (Project ÒRÉ), which was delivered to groups of 3 to 8 adolescents who were members of the same friendship network. Sixteen focus groups ( N = 63) were conducted with youth following their participation in the intervention. Results demonstrate high acceptability of the intervention. Both males and females revealed multiple benefits of attending the intervention with friends including feeling more comfortable, experiencing general satisfaction with the program, experiencing greater ease in talking and expressing self, being able to reveal sensitive information, and being able to relate to each other’s experiences. Additional themes were presented only by males including feeling a sense of cohesion, the ability to protect each other from HIV/STIs in the future, and feeling safe. These results suggest that delivering HIV/STI and other prevention interventions within adolescents’ friendship networks may offer unique benefits not found with traditional programs that include random groupings of youth who are not familiar with each other.
Strong Variability of Di(2‐ethylhexyl)phthalate (DEHP) Plasmatic Rate in Infants and Children Undergoing 12‐Hour Cyclic Parenteral Nutrition
Authors: Kambia Nicolas , Dine Thierry , Gressier Bernard , Luyckx Michel , Brunet Claude , Guimber Dominique , Turck Dominique , Gottrand Frederic , Michaud Laurent
Published: June 2012

Background: Medical devices such as perfusion materials in polyvinyl chloride may contain di(2‐ethylhexyl)phthalate (DEHP). Several studies have questioned the harmlessness of phthalates, which have been shown to have toxic effects on the reproductive system and general development. This study was designed to assess DEHP exposure in infants and children benefitting from cyclic parenteral nutrition (PN). The results are compared with those obtained from children used as controls and receiving no PN, to estimate the potential risk to this pediatric population, taking into account exposure levels and already published data. Methods: Plasmatic concentrations of DEHP were assessed by high‐performance liquid chromatography from blood samples taken from 22 children at the start and finish of a 12‐hour cyclic PN period and compared with those obtained from 20 control children of comparable age and gender. Results: After a 12‐hour cyclic PN period, DEHP migration varied widely among the patients. The concentrations were not quantifiable in 4 children at the start of PN. In 1 child, they were quantifiable neither at the start nor at the end of PN. However, for 17 children, DEHP concentrations were quantifiable at the start of PN and were very variable from one child to another. At the end, DEHP concentrations had significantly but variably increased in these children. No trace of DEHP was found in the blood samples from 20 healthy controls. Conclusion: Considering published data on phthalate toxicity, it would appear advisable to encourage the use of medical devices that are either phthalate or DEHP free.
Maternal Union Transitions and Household Food Insecurity
Authors: Hernandez Daphne C. , Pressler Emily
Published: June 2012

The study investigates how transitions in maternal unions are related to household food insecurity among a low-income sample using pooled time series data from the Early Childhood Longitudinal Survey–Birth Cohort. Pooled time series fixed effects models indicate that transitioning into unions for White and Hispanic households is associated with reductions in household food insecurity compared with White and Hispanic households who experienced no transitions. Furthermore, transitioning into unions for Hispanic households is associated with reductions in household food insecurity status compared with Hispanic households that experienced dissolving unions. Last, results indicate that maternal union transitions are not related to household food insecurity status of Black and Other race and ethnic households. The authors discuss how the findings may be related to socioeconomic factors of race and ethnic households.
Evaluation of the Maquet Neonatal and Pediatric Quadrox I with an integrated arterial line filter during cardiopulmonary bypass
Authors: Melchior RW , Schiavo K , Frey T , Rogers D , Patel J , Chelnik K , Rosenthal T
Published: June 2012

Background:

Perfusion equipment has evolved since its introduction into clinical practice more than fifty years ago to include smaller cardiopulmonary bypass (CPB) circuits and components. Perfusionists are now exploring the function of new oxygenators with an integrated arterial line filter (IALF). The purpose of this trial was to examine the Maquet Quadrox-I Neonatal and Pediatric oxygenators with IALF in a clinical setting, with respect to gas transfer, heat exchange co-efficiency (HEC), trans-membrane pressure (TMP) gradient and clinical experience.

Methods:

The Maquet Quadrox-I Neonatal oxygenator was used on 30 patients ranging from 2.2-13.1 kg. The Maquet Quadrox-I Pediatric oxygenator was used on 15 patients ranging from 12.7-24.5 kg. Arterial and venous blood gases were taken once the patient was stable on CPB and, subsequently, every 30 minutes afterwards, as per institution protocol. The values for gas transfer rates, HEC and TMP gradient were stratified into three main categories with each oxygenator: normothermia, cooling and re-warming.

Results:

During all conditions, the gas transfer rate with both oxygenators was efficient. The HEC values showed efficient heat exchanger performance during all conditions with both oxygenators. While maintaining CPB flow within the manufacturer’s recommended flow rate for each oxygenator, the TMP gradient range for the Neonatal Quadrox-I was 10-40 mmHg and the Pediatric Quadrox-I was 10-60 mmHg. During the clinical trial, foam was shown to break through the cardiotomy on several occasions when high sucker return was required.

Conclusion:

This new line of oxygenators performed well with regards to gas transfer, HEC and TMP gradient, but there were clinical experiences that did not meet expectations. There were repeated incidences with the venous reservoir which ultimately cast a negative light on the design of this new product from Maquet. In the future, the authors would like to evaluate updated versions of this product from Maquet and any other pediatric perfusion devices that could help the patient in the clinical arena.
Granulocyte Colony Stimulating Factor (G-CSF) can allow treatment with clozapine in a patient with severe Benign Ethnic Neutropaenia (BEN): a case report
Authors: Spencer Benjamin WJ , Williams Hugh RJ , Gee Siobhan H , Whiskey Eromona , Rodrigues Joseph P , Mijovic Aleksandar , MacCabe James H
Published: June 2012

Clozapine is the treatment of choice for treatment-resistant schizophrenia, but it is associated with a risk of neutropaenia and agranulocytosis. Clozapine use is regulated by mandatory blood monitoring in the UK, requiring cessation of treatment should the absolute neutrophil count (ANC) drop below specified values. Benign reductions in the ANC in non-white populations are common, and this can preclude a patient from receiving treatment with clozapine. A diagnosis of benign ethnic neutropaenia can reduce these treatment restrictions (UK specific), but the degree of neutropaenia can be significant enough to still prevent treatment. In this report, we show that response to granulocyte colony stimulating factor (G-CSF) may be quite variable and difficult to predict, but with careful monitoring it can be used to increase the ANC count and allow continued treatment with clozapine.
Influence of the addition of lubricant on the properties of poly(ether ether ketone)/basalt fiber composites
Authors: Wang Hongsong , Wang Guibin , Zhang Limei , Jiang Zhenhua , Guan Shaowei , Zhang Shuling
Published: June 2012

Improvement in the processability of poly(ether ether ketone)/basalt fiber (PEEK/BF) composites with less influence on other properties is important. A novel high-temperature lubricant GENIOPLAST PELLETS (GPPS) was used in order to decrease the melt viscosity of PEEK/BF composites. The compounds of PEEK/BF/GPPS were characterized by torque of screw, universal tester, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA). The results showed that a small amount of GPPS could greatly decrease melt viscosity of the composites during processing, and improve the dispersion uniformity and orientation of BF in the PEEK matrix, followed by the enhancement of the modulus and strength of PEEK/BF composites, meanwhile the thermal stability of the compounds was almost unaffected.
Synthesis, characterization and thermal degradation of phosphorus–nitrogen containing poly(aryl ether ketone)s
Authors: Xie Xuexia , Wang Zhou , Zhang Kun , Xu Jing
Published: June 2012

A series of high-molecular-weight poly(aryl ether ketone)s with phosphorus and nitrogen on their side and main chains was synthesized by a nucleophilic substitution polycondensation of 6-(4-hydroxyphenyl)pyridazin-3(2 H)-one (HPZ) with 1,1′-bis(4-hydroxyphenyl)-metheylene-bispheny-1-oxophosphine oxide (DOPO-PhOH) and 4, 4′-difluorobenzophenone (DFBP) at various molar ratios. The structures of the poly(aryl ether ketone)s were characterized by means of Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR, 31P NMR) and elemental analysis. The influence of the nitrogen- and phosphorus-containing monomer ratio on their thermal stability was investigated by adjusting the proportion of the HPZ and DOPO–PhOH from 0:10 to 8:2. The polymers were readily soluble in polar organic solvents, such as N-methylpyrrolidone (NMP), N, N-dimethylacetamide (DMAc), N, N-dimethylformamide (DMF) and chloroform. Differential scanning calorimetry (DSC) demonstrated that these polymers have an amorphous morphology.
Influence of foam structure and service environment on sound absorption characteristics of polyimide foams
Authors: Liu Xiao-Yan , Zhan Mao-Sheng , Wang Kai
Published: June 2012

The sound absorption properties of open-celled polyimide foams at room temperature and high temperatures were tested by an AWA6122A standing wave tube and a temperature controllable impedance tube, respectively. The sound absorption characteristics of polyimide foams at room temperature were analyzed by applying the rigid end model and Helmholtz resonator model. The effects of material structures (thickness, density and cell size) and material service environments (frequency of sound wave, ambient temperature and mechanical crushing) on the sound absorption coefficients ( α) were investigated. The results showed that the models can predict the numerical relationship between the structure parameters and α. At frequencies below 1600 Hz the value of α increased with the increase of foam thickness and foam density and decreased with the increase of cell size. In contrast to untreated polyimide foams, the first resonant frequencies of mechanically crushed polyimide foams moved to higher frequencies and αincreased at higher frequencies. With an increase in temperature, at the same frequencies below 2000 Hz, the αof polyimide foams decreased and the first resonant frequencies trended to move towards higher frequencies. The experimental data indicated that the sound absorption properties of polyimide foams were significantly influenced by foam structures and service environments.
The Association of CYP2D6 Genotype and Postoperative Nausea and Vomiting in Orthopedic Trauma Patients
Authors: Wesmiller Susan W. , Henker Richard A. , Sereika Susan M. , Donovan Heidi S. , Meng Li , Gruen Gary S. , Tarkin Ivan S. , Conley Yvette P.
Published: June 2012

The CYP2D6 gene encodes for an enzyme that is involved in the metabolism of more than 25% of all medications, including many opioids and antiemetics. It may contribute to the risk of postoperative nausea and vomiting (PONV), a common surgical complication. However, little research has been conducted in this area. The purpose of this study was to explore the association of CYP2D6 genotypes with PONV in adult surgical trauma patients. Data from 112 patients (28% female) with single extremity fractures, aged 18–70 years, were analyzed. PONV was defined as present if patients reported nausea, were observed vomiting, or received medication for PONV. Saliva samples collected for DNA extraction and Taqman® allele discrimination and quantitative real time polymerase chain reaction (qRT-PCR) were used to collect genotype data that were then used to assign CYP2D6 phenotype classification. The incidence of PONV was 38% in the postanesthesia care unit and increased to 50% when assessed at 48 hr. CYP2D6 classification results were 7 (6%) poor metabolizers, 34 (30%) intermediate metabolizers, and 71 (63%) extensive metabolizers. No ultrarapid metabolizers were identified. Patients who were classified as poor metabolizers had less PONV and higher pain scores. Gender and history of PONV, but not smoking, were also significant risk factors. Findings suggest variability in CYP2D6 impacts susceptibility to PONV.
Strange but common bedfellows: The relationship between humanitarians and the military in developing psychosocial interventions for civilian populations affected by armed conflict
Authors: Kienzler Hanna , Pedersen Duncan
Published: June 2012

This essay analyses how the relationships between Cold War and post-Cold War politics, military psychiatry, humanitarian aid and mental health interventions in war and post-war contexts have transformed over time. It focuses on the restrictions imposed on humanitarian interventions and aid during the Cold War; the politics leading to the transfer of the PTSD diagnosis and its treatment from the military to civilian populations; humanitarian intervention campaigns in the post-Cold War era; and the development of psychosocial intervention programs and standards of care for civilian populations affected by armed conflict. Viewing these developments in their broader historical, political and social contexts reveals the politics behind mental health interventions conducted in countries and populations affected by warfare. In such militarized contexts, the work of NGOs providing assistance to people suffering from trauma-related health problems is far from neutral as it depends on the support of the military and plays an important role in the shaping of international politics and humanitarian aid programs.
Graduated Exposure, Positive Reinforcement, and Stimulus Distraction in a Compliance-With-Blood-Draw Intervention for an Adult With Autism
Authors: Grider Blake , Luiselli James K. , Turcotte-Shamski William
Published: June 2012

The authors report the case of a 21-year-old man who had autism and feared having his blood drawn as a required medical procedure. He was first exposed to simulated blood draws during a baseline phase and subsequently an intervention phase that (a) gradually exposed him to the procedures that constituted a blood draw, (b) reinforced his compliant behavior, and (c) provided stimulus distraction. He successfully completed intervention and tolerated actual blood draws 1 month and 4 months later. The authors discuss clinical and research issues when conducting intervention for medical fears among people who have intellectual and developmental disabilities.
All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)
Authors: Iland Harry J. , Bradstock Ken , Supple Shane G. , Catalano Alberto , Collins Marnie , Hertzberg Mark , Browett Peter , Grigg Andrew , Firkin Frank , Hugman Amanda , Reynolds John , Di Iulio Juliana , Tiley Campbell , Taylor Kerry , Filshie Robin , Seldon Michael , Taper John , Szer Jeff , Moore John , Bashford John , Seymour John F.
Published: June 2012

The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all-trans-retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification (P[trend] = .03). Compared with our previously reported ATRA/idarubicin-based protocol (APML3), APML4 patients had statistically significantly improved freedom from relapse (P = .006) and failure-free survival (P = .01). In conclusion, the use of ATO in both induction and consolidation achieved excellent outcomes despite a substantial reduction in anthracycline exposure. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12605000070639.