bluuebunny/crossref_metadata_2025 huggingface dataset:
Eavesdropping on the Mob: the functional diversification of Mafia activities across territories
Authors: Campana Paolo
Published: May 2011

How do Mafias operate across territories? The paper is an in-depth study of the operations of a Neapolitan Camorra group. It relies on a unique data set of contacts manually extracted from the transcripts of phone conversations wiretapped by the police. The data show that the clan is indeed involved in the production and supply of extra-legal protection, but only in its territory of origin. The expansion abroad followed the lines of a functional diversification: branches were created to carry out specific activities but no large-scale international alliances were forged. The strategies underpinning the group’s operations differ greatly across territories. Overall, the clan is still highly dependent on the territory of origin. Finally, the paper argues against the concept of ‘transnational organized crime’ and proposes a new taxonomy that better accounts for the ways in which Mafia groups choose to operate outside their territories of origin.
Predicting adult violent delinquency: Gender differences regarding the role of childhood behaviour
Authors: Reef Joni , Donker Andrea G. , Van Meurs Inge , Verhulst Frank C. , Van Der Ende Jan
Published: May 2011

Adult violent delinquency harms individuals, their families and society at large. Knowledge about childhood predictors of adult delinquency could be helpful in defining at-risk children who will develop into violent adults. This topic is rarely investigated in females. We investigated which behavioural problems in childhood predicted long-term disruptive development in a sample of both males and females. In 1983, behaviour problems were assessed in a community sample of 2076 children; 24 years later, 1335 of these children, who are now adults, reported on their violent delinquency. Girls with conduct problems were at risk of long-term disruptive development. We recommend that health professionals be alert regarding girls with conduct problems, because early identification and treatment of high-risk girls might reduce delinquency in adult life.
The History and Future of Assessment for Effective Intervention
Authors: Hosp John L. , Watt Sarah
Published: May 2011

Assessment for Effective Intervention ( AEI) has been published for more than 36 years encompassing 90 issues and 615 articles. The topics and trends of these articles have varied by decade. Notably, the period of 2000 to 2010 was a very productive time for the journal. This article introduces the new editorial team, summarizes the trend of topics and formats, and provides a brief history of AEI before presenting the format and goals of the near future for AEI.
Purged: Undocumented Students, Financial Aid Policies, and Access to Higher Education
Authors: Diaz-Strong Daysi , Gómez Christina , Luna-Duarte Maria E. , Meiners Erica R.
Published: May 2011

This article examines how the denial of financial aid constrains undocumented students from pursuing higher education and discusses the interlocking relationship between federal immigration and higher education policies. Reporting on research data identifying that undocumented students pay for their education through work, family contributions, few scholarships, and strategies such as working more and taking fewer classes, this article also links the stress placed on undocumented students and their families to Latino retention and graduation rates.
Identifying Predictors of College Success Through an Examination of AVID Graduates’ College Preparatory Achievements
Authors: Watt Karen M. , Huerta Jeffery J. , Alkan Ersan
Published: May 2011

This mixed-methods research investigates the high school college preparatory achie vements and college success of 50 high school graduates who participated in Advancement Via Individual Determination (AVID) and belonged to groups underrepresented in higher education. High performance on the Texas Assessment of Knowledge and Skills (TAKS) and acquiring college credits while in high school were found to be significant predictors of college success. In addition, AVID support and strategies contributed to students’ transition into college.
Safety, Tolerability, and Pharmacokinetics of KP-1461 in Phase I Clinical Studies
Authors: Clay Patrick G. , McRae MaryPeace , Laurent Jean-Pierre
Published: May 2011

Background: KP-1461 is a prodrug to KP-1212. KP-1212 is a viral mutagen designed to increase viral error rate. Methods: We describe 2 phase I studies: KP1461-101 (double-blind, placebo-controlled, single, escalating doses, 100 to 1600 mg study in 42 non-HIV-infected participants) and KP-1461-102 (double-blind placebo-controlled dose escalation 14-day study in HIV-infected participants, 400-3200 mg). Primary objectives were safety/tolerability. Secondary objectives included pharmacokinetic analysis with exploratory objective to characterize KP-1212 effects on viral load. Results: KP-1461 was well tolerated. Majority of adverse events were grade 1 (neurological, gastrointestinal, cardiovascular). Four participants experienced grade 3 and 1 experienced a grade 4 event. Analysis demonstrated no difference in pharmacokinetic parameters at day 1 or 14. Linear pharmacokinetics found in 1600 mg arm. Compared to placebo, only at the 3200 mg dose demonstrated a marginally statistically significant virologic response. Conclusions: These studies provide safety/tolerability information and suggest virologic efficacy. KP-1212, a first-in-class antiretroviral, demonstrates the ability to induce viral eradication in vitro. Viral reduction in vivo may foretell a paradigm shift in HIV pharmacotherapy.
Bayesian Versus Orthodox Statistics: Which Side Are You On?
Authors: Dienes Zoltan
Published: May 2011

Researchers are often confused about what can be inferred from significance tests. One problem occurs when people apply Bayesian intuitions to significance testing—two approaches that must be firmly separated. This article presents some common situations in which the approaches come to different conclusions; you can see where your intuitions initially lie. The situations include multiple testing, deciding when to stop running participants, and when a theory was thought of relative to finding out results. The interpretation of nonsignificant results has also been persistently problematic in a way that Bayesian inference can clarify. The Bayesian and orthodox approaches are placed in the context of different notions of rationality, and I accuse myself and others as having been irrational in the way we have been using statistics on a key notion of rationality. The reader is shown how to apply Bayesian inference in practice, using free online software, to allow more coherent inferences from data.
Statistical Evidence in Experimental Psychology
Authors: Wetzels Ruud , Matzke Dora , Lee Michael D. , Rouder Jeffrey N. , Iverson Geoffrey J. , Wagenmakers Eric-Jan
Published: May 2011

Statistical inference in psychology has traditionally relied heavily on p-value significance testing. This approach to drawing conclusions from data, however, has been widely criticized, and two types of remedies have been advocated. The first proposal is to supplement p values with complementary measures of evidence, such as effect sizes. The second is to replace inference with Bayesian measures of evidence, such as the Bayes factor. The authors provide a practical comparison of p values, effect sizes, and default Bayes factors as measures of statistical evidence, using 855 recently published t tests in psychology. The comparison yields two main results. First, although p values and default Bayes factors almost always agree about what hypothesis is better supported by the data, the measures often disagree about the strength of this support; for 70% of the data sets for which the p value falls between .01 and .05, the default Bayes factor indicates that the evidence is only anecdotal. Second, effect sizes can provide additional evidence to p values and default Bayes factors. The authors conclude that the Bayesian approach is comparatively prudent, preventing researchers from overestimating the evidence in favor of an effect.
Is the patient’s baseline inhaled steroid dose a factor for choosing the budesonide/formoterol maintenance and reliever therapy regimen?
Authors: Aubier Michel , Haughney John , Selroos Olof , van Schayck Onno C. P. , Ekström Tommy , Ostinelli Juliette , Buhl Roland
Published: May 2011

Objective: Baseline inhaled corticosteroid (ICS) dose may be a factor for prescribers to consider when they select a budesonide/formoterol maintenance and reliever therapy regimen for symptomatic asthmatics.

Methods: A 6-month randomized study compared two maintenance doses of budesonide/formoterol 160/4.5 µg, 1 × 2 and 2 × 2, plus as needed, in 8424 asthma patients with symptoms when treated with ICS ± an inhaled long-acting β2-agonist (LABA). In the total study population, 1339 (17%) were high-dose ICS (HD) users (≥1600 µg/day budesonide). This HD stratum was compared with the rest of the study population, divided into low-dose (LD; 400 µg/day) and medium-dose strata (MD; 401–1599 µg/day) with regard to severe asthma exacerbations and mean changes in five-item Asthma Control Questionnaire (ACQ5) scores from baseline.

Results: In all three strata there were fewer exacerbations in the 2 × 2 treatment groups (yearly rates 0.268, 0.172 and 0.094) than in the 1 × 2 treatment groups (yearly rates 0.232, 0.138 and 0.764). In no stratum was the difference between the treatment groups statistically significant. There was no statistically significant difference in time to the first severe exacerbation between the treatments 2 × 2 and 1 × 2 in the HD group (hazard ratio 0.944, p = 0.75). The adjusted mean changes in ACQ5 scores in the HD, MD and LD strata were −0.89, −0.61 and −0.65, respectively, with 1 × 2 treatment and −0.90, −0.74 and −0.76, respectively, with 2 × 2 treatment. In the MD and LD strata, the difference between doses was significant in favour of 2 × 2 (MD p < 0.0001; LD p = 0.004), but not in the HD stratum ( p = 0.870). No difference in serious adverse events was seen.

Conclusion: Compared with the LD and MD strata, the HD stratum patients had more exacerbations and a shorter time to first exacerbation. However, there were no differences in response between the 1 × 2 and 2 × 2 groups in any of the strata. This indicates that patients using budesonide/formoterol maintenance and reliever therapy, irrespective of baseline ICS dose, can be switched to 1 × 2 with its lower steroid load. ACQ5 scores improved more in the HD stratum than in the MD and LD strata indicating, among other things, that HD patients were not overtreated at baseline.

ClinicalTrials.gov registration: NCT00463866
Hey Mom, What’s on Your Facebook? Comparing Facebook Disclosure and Privacy in Adolescents and Adults
Authors: Christofides Emily , Muise Amy , Desmarais Serge
Published: May 2011

People of all ages are increasingly exposed to online environments that encourage them to share and connect with others. However, there is a perception that adolescents are particularly susceptible to these cues and share more online than do other age groups. With a group of 288 adolescents and 285 adults, we explored differences and similarities in use of Facebook for information sharing and use of the controls to protect their privacy. Adolescents reported disclosing more information on Facebook and using the privacy settings less than adults. Despite these differences, the results indicated that adolescents and adults were more similar than different in the factors that predicted information disclosure and control. Adolescents spent more time on Facebook, which partially mediated the relationship between group (adolescents vs. adults) and disclosure. Self-esteem partially mediated the relationship between group and information control, with adults having higher self-esteem than adolescents.
Parallels in the Beliefs and Works of Margaret Fuller and Carl Jung
Authors: Aldridge Jerry , Kilgo Jennifer L. , Werner Melissa , Christensen Lois M.
Published: May 2011

Margaret Fuller, the 19th-century feminist and Transcendentalist, has been compared with Louisa May Alcott, Ralph Waldo Emerson, Nathaniel Hawthorne, and Henry David Thoreau. The life and theories of Carl Jung, the 20th-century psychiatrist, have been compared with the works of Sigmund Freud, Alfred Adler, Jean Piaget, and Sabina Spielrein among others. However, no comparisons have been published concerning the beliefs and works of Fuller and Jung. The purpose of this research was to compare and contrast the beliefs and written works of Margaret Fuller and Carl Jung. Similarities and differences were reported among their ideologies. Similarities in their childhood and adult dreams, literary references, spiritual beliefs, and explorations of gender were described. Differences were reported, which included the focus of their writings and their ideas about who is to blame when things go wrong, and how to deal with the individual daemon in each person was also explored. Special consideration was given to how closely their writings intersect. Specifically, the authors questioned whether Jung was inspired by the ideas and writings of Fuller. To answer this question, five possibilities were identified.
Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report
Authors: Miller Weston P. , Rothman Steven M. , Nascene David , Kivisto Teresa , DeFor Todd E. , Ziegler Richard S. , Eisengart Julie , Leiser Kara , Raymond Gerald , Lund Troy C. , Tolar Jakub , Orchard Paul J.
Published: May 2011

Cerebral adrenoleukodystrophy (cALD) remains a devastating neurodegenerative disease; only allogeneic hematopoietic cell transplantation (HCT) has been shown to provide long-term disease stabilization and survival. Sixty boys undergoing HCT for cALD from 2000 to 2009 were analyzed. The median age at HCT was 8.7 years; conditioning regimens and allograft sources varied. At HCT, 50% demonstrated a Loes radiographic severity score ≥ 10, and 62% showed clinical evidence of neurologic dysfunction. A total of 78% (n = 47) are alive at a median 3.7 years after HCT. The estimate of 5-year survival for boys with Loes score < 10 at HCT was 89%, whereas that for boys with Loes score ≥ 10 was 60% (P = .03). The 5-year survival estimate for boys absent of clinical cerebral disease at HCT was 91%, whereas that for boys with neurologic dysfunction was 66% (P = .08). The cumulative incidence of transplantation-related mortality at day 100 was 8%. Post-transplantation progression of neurologic dysfunction depended significantly on the pre-HCT Loes score and clinical neurologic status. We describe the largest single-institution analysis of survival and neurologic function outcomes after HCT in cALD. These trials were registered at www.clinicaltrials.gov as #NCT00176904, #NCT00668564, and #NCT00383448.
FunFOLD: an improved automated method for the prediction of ligand binding residues using 3D models of proteins
Authors: Roche Daniel B , Tetchner Stuart J , McGuffin Liam J
Published: May 2011

Background

The accurate prediction of ligand binding residues from amino acid sequences is important for the automated functional annotation of novel proteins. In the previous two CASP experiments, the most successful methods in the function prediction category were those which used structural superpositions of 3D models and related templates with bound ligands in order to identify putative contacting residues. However, whilst most of this prediction process can be automated, visual inspection and manual adjustments of parameters, such as the distance thresholds used for each target, have often been required to prevent over prediction. Here we describe a novel method FunFOLD, which uses an automatic approach for cluster identification and residue selection. The software provided can easily be integrated into existing fold recognition servers, requiring only a 3D model and list of templates as inputs. A simple web interface is also provided allowing access to non-expert users. The method has been benchmarked against the top servers and manual prediction groups tested at both CASP8 and CASP9.

Results

The FunFOLD method shows a significant improvement over the best available servers and is shown to be competitive with the top manual prediction groups that were tested at CASP8. The FunFOLD method is also competitive with both the top server and manual methods tested at CASP9. When tested using common subsets of targets, the predictions from FunFOLD are shown to achieve a significantly higher mean Matthews Correlation Coefficient (MCC) scores and Binding-site Distance Test (BDT) scores than all server methods that were tested at CASP8. Testing on the CASP9 set showed no statistically significant separation in performance between FunFOLD and the other top server groups tested.

Conclusions

The FunFOLD software is freely available as both a standalone package and a prediction server, providing competitive ligand binding site residue predictions for expert and non-expert users alike. The software provides a new fully automated approach for structure based function prediction using 3D models of proteins.
CASCADE_SCAN: mining signal transduction network from high-throughput data based on steepest descent method
Authors: Wang Kai , Hu Fuyan , Xu Kejia , Cheng Hua , Jiang Meng , Feng Ruili , Li Jing , Wen Tieqiao
Published: May 2011

Background

Signal transduction is an essential biological process involved in cell response to environment changes, by which extracellular signaling initiates intracellular signaling. Many computational methods have been generated in mining signal transduction networks with the increasing of high-throughput genomic and proteomic data. However, more effective means are still needed to understand the complex mechanisms of signaling pathways.

Results

We propose a new approach, namely CASCADE_SCAN, for mining signal transduction networks from high-throughput data based on the steepest descent method using indirect protein-protein interactions (PPIs). This method is useful for actual biological application since the given proteins utilized are no longer confined to membrane receptors or transcription factors as in existing methods. The precision and recall values of CASCADE_SCAN are comparable with those of other existing methods. Moreover, functional enrichment analysis of the network components supported the reliability of the results.

Conclusions

CASCADE_SCAN is a more suitable method than existing methods for detecting underlying signaling pathways where the membrane receptors or transcription factors are unknown, providing significant insight into the mechanism of cellular signaling in growth, development and cancer. A new tool based on this method is freely available at http://www.genomescience.com.cn/CASCADE_SCAN/.
AGE-BSA down-regulates endothelial connexin43 gap junctions
Authors: Wang Chi-Young , Liu Hung-Jen , Chen Heng-Ju , Lin Yi-Chun , Wang Hsueh-Hsiao , Hung Ta-Chuan , Yeh Hung-I
Published: May 2011

Background

Advanced glycation end products generated in the circulation of diabetic patients were reported to affect the function of vascular wall. We examined the effects of advanced glycation end products-bovine serum albumin (AGE-BSA) on endothelial connexin43 (Cx43) expression and gap-junction communication.

Results

In human aortic endothelial cells (HAEC) treated with a series concentrations of AGE-BSA (0-500 μg/ml) for 24 and 48 hours, Cx43 transcript and Cx43 protein were reduced in a dose dependent manner. In addition, gap-junction communication was reduced. To clarify the mechanisms underlying the down-regulation, MAPKs pathways in HAEC were examined. Both a MEK1 inhibitor (PD98059) and a p38 MAPK inhibitor (SB203580) significantly reversed the reductions of Cx43 mRNA and protein induced by AGE-BSA. Consistently, phosphorylation of ERK and p38 MAPK was enhanced in response to exposure to AGE-BSA. However, all reversions of down-regulated Cx43 by inhibitors did not restore the functional gap-junction communication.

Conclusions

AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.
Correct anteroposterior patterning of the zebrafish neurectoderm in the absence of the early dorsal organizer
Authors: Varga Máté , Maegawa Shingo , Weinberg Eric S
Published: May 2011

Background

The embryonic organizer (i.e., Spemann organizer) has a pivotal role in the establishment of the dorsoventral (DV) axis through the coordination of BMP signaling. However, as impaired organizer function also results in anterior and posterior truncations, it is of interest to determine if proper anteroposterior (AP) pattern can be obtained even in the absence of early organizer signaling.

Results

Using the ventralized, maternal effect ichabod (ich) mutant, and by inhibiting BMP signaling in ich embryos, we provide conclusive evidence that AP patterning is independent of the organizer in zebrafish, and is governed by TGFβ, FGF, and Wnt signals emanating from the germ-ring. The expression patterns of neurectodermal markers in embryos with impaired BMP signaling show that the directionality of such signals is oriented along the animal-vegetal axis, which is essentially concordant with the AP axis. In addition, we find that in embryos inhibited in both Wnt and BMP signaling, the AP pattern of such markers is unchanged from that of the normal untreated embryo. These embryos develop radially organized trunk and head tissues, with an outer neurectodermal layer containing diffusely positioned neuronal precursors. Such organization is reflective of the presumed eumetazoan ancestor and might provide clues for the evolution of centralization in the nervous system.

Conclusions

Using a zebrafish mutant deficient in the induction of the embryonic organizer, we demonstrate that the AP patterning of the neuroectoderm during gastrulation is independent of DV patterning. Our results provide further support for Nieuwkoop's "two step model" of embryonic induction. We also show that the zebrafish embryo can form a radial diffuse neural sheath in the absence of both BMP signaling and the early organizer.
Genome-wide profiling of G protein-coupled receptors in cerebellar granule neurons using high-throughput, real-time PCR
Authors: Maurel Benjamin , Le Digarcher Anne , Dantec Christelle , Journot Laurent
Published: May 2011

Background

G protein-coupled receptors (GPCRs) are major players in cell communication, regulate a whole range of physiological functions during development and throughout adult life, are affected in numerous pathological situations, and constitute so far the largest class of drugable targets for human diseases. The corresponding genes are usually expressed at low levels, making accurate, genome-wide quantification of their expression levels a challenging task using microarrays.

Results

We first draw an inventory of all endo-GPCRs encoded in the murine genome. To profile GPCRs genome-wide accurately, sensitively, comprehensively, and cost-effectively, we designed and validated a collection of primers that we used in quantitative RT-PCR experiments. We experimentally validated a statistical approach to analyze genome-wide, real-time PCR data. To illustrate the usefulness of this approach, we determined the repertoire of GPCRs expressed in cerebellar granule neurons and neuroblasts during postnatal development.

Conclusions

We identified tens of GPCRs that were not detected previously in this cell type; these GPCRs represent novel candidate players in the development and survival of cerebellar granule neurons. The sequences of primers used in this study are freely available to those interested in quantifying GPCR expression comprehensively.
Fosmid library end sequencing reveals a rarely known genome structure of marine shrimp Penaeus monodon
Authors: Huang Shiao-Wei , Lin You-Yu , You En-Min , Liu Tze-Tze , Shu Hung-Yu , Wu Keh-Ming , Tsai Shih-Feng , Lo Chu-Fang , Kou Guang-Hsiung , Ma Gwo-Chin , Chen Ming , Wu Dongying , Aoki Takashi , Hirono Ikuo , Yu Hon-Tsen
Published: May 2011

Background

The black tiger shrimp (Penaeus monodon) is one of the most important aquaculture species in the world, representing the crustacean lineage which possesses the greatest species diversity among marine invertebrates. Yet, we barely know anything about their genomic structure. To understand the organization and evolution of the P. monodon genome, a fosmid library consisting of 288,000 colonies and was constructed, equivalent to 5.3-fold coverage of the 2.17 Gb genome. Approximately 11.1 Mb of fosmid end sequences (FESs) from 20,926 non-redundant reads representing 0.45% of the P. monodon genome were obtained for repetitive and protein-coding sequence analyses.

Results

We found that microsatellite sequences were highly abundant in the P. monodon genome, comprising 8.3% of the total length. The density and the average length of microsatellites were evidently higher in comparison to those of other taxa. AT-rich microsatellite motifs, especially poly (AT) and poly (AAT), were the most abundant. High abundance of microsatellite sequences were also found in the transcribed regions. Furthermore, via self-BlastN analysis we identified 103 novel repetitive element families which were categorized into four groups, i.e., 33 WSSV-like repeats, 14 retrotransposons, 5 gene-like repeats, and 51 unannotated repeats. Overall, various types of repeats comprise 51.18% of the P. monodon genome in length. Approximately 7.4% of the FESs contained protein-coding sequences, and the Inhibitor of Apoptosis Protein (IAP) gene and the Innexin 3 gene homologues appear to be present in high abundance in the P. monodon genome.

Conclusions

The redundancy of various repeat types in the P. monodon genome illustrates its highly repetitive nature. In particular, long and dense microsatellite sequences as well as abundant WSSV-like sequences highlight the uniqueness of genome organization of penaeid shrimp from those of other taxa. These results provide substantial improvement to our current knowledge not only for shrimp but also for marine crustaceans of large genome size.
Mortality and associated risk factors in a cohort of tuberculosis patients treated under DOTS programme in Addis Ababa, Ethiopia
Authors: Getahun Belete , Ameni Gobena , Biadgilign Sibhatu , Medhin Girmay
Published: May 2011

Background

Tuberculosis (TB) is the leading cause of mortality among infectious diseases worldwide. Ninty five percent of TB cases and 98% of deaths due to TB occur in developing countries. Globally, the mortality rate has declined with the introduction of effective anti TB chemotherapy. Nevertheless, some patients with active TB still die while on treatment for their disease. In Ethiopia, little is known on survival and risk factors for mortality among a cohort of TB patients. The objective of the study is to determine the magnitude and identify risk factors associated with time to death among TB patients treated under DOTS programme in Addis Ababa, Ethiopia.

Methods

This is a retrospective cohort study. Data was obtained by assessing medical records of TB patients registered from June 2004 to July 2009 G.C and treated under the DOTS strategy in three randomly selected health centers. A step-wise multivariable Cox's regression model and Kaplan- Meier curves were used to model the outcome of interest. Mortality was used as an outcome measure. Person-years of observation (PYO) were calculated from the date of starting anti-TB treatment to date of outcome and was calculated as the number of deaths/100 PYO. Statistical analysis SPSS version 16 was used for data analysis and results were reported significant whenever P-value was less than 5%.

Results

From a total of 6,450 registered TB patients 236(3.7%) were died. More than 75% death occurred within eight month of treatment initiation. The mean and median times of survival starting from the date of treatment initiation were 7.2 and 7.9 months, respectively. Comparison of survival curves using Kaplan Meier curves method with log-rank test showed that the survival status was significantly different between patient categories as well as across treatment centers (P < 0.05). The death rate of pulmonary positive, pulmonary negative and extra pulmonary TB patients were 2.7%, 3.6%, and 4.3%, respectively. Body weight at initiation of anti-TB treatment (<35 kg), patient category, year of enrollment and treatment center were independent predictors for time to death.

Conclusions

Most of the patients were died at the end of treatment period. This underlines the need for devising a mechanism of standardizing the existing DOTS programme and nutritional support for underweight patients for better clinical and treatment outcome.
Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey
Authors: Lin Yilan , Huang Lijuan , Nie Shaofa , Liu Zengyan , Yu Hongjie , Yan Weirong , Xu Yihua
Published: May 2011

Background

China is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks.

Methods

A close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method.

Results

30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the state's priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23).

Conclusions

This A/H1N1 epidemic has not caused public panic yet, but the knowledge of A/H1N1 in residents is not optimistic. Public education campaign may take the side effects of vaccine and the knowledge about the state's vaccination strategy into account.
Germ-line mutations in epidermal growth factor receptor (EGFR) are rare but may contribute to oncogenesis: A novel germ-line mutation in EGFR detected in a patient with lung adenocarcinoma
Authors: Centeno Irene , Blay Pilar , Santamaría Iñigo , Astudillo Aurora , Pitiot Ana S , Osorio Fernando G , González-Arriaga Patricia , Iglesias Fernando , Menéndez Primitiva , Tardón Adonina , Freije Jose M , Balbín Milagros
Published: May 2011

Background

A subset of lung cancer patients harbour EGFR somatic mutations in their tumours and are candidates for treatment with EGFR tyrosine kinase inhibitors. In a few cases EGFR mutations have also been found in the germ line, suggesting a role in lung carcinogenesis. Objetives of this study were: 1) To analyze the EGFR gene mutations in a population diagnosed with lung adenocarcinoma from Northern Spain. 2) To determine the frequency of a new germ-line mutation found in our laboratory as well as the frequency in our population of three other EGFR germ-line mutations detected by other authors. 3) To determine whether the novel mutation detected may have a functional effect on the EGFR protein.

Methods

Tumour DNA samples were obtained from frozen or paraffin embedded tumour tissues. Samples of DNA from peripheral blood cells were obtained from 912 individuals with lung cancer recruited from the CAPUA study [1, 2], 477 unrelated healthy donor individuals and 32 individuals with other types of cancer. EGFR gene exons 18 to 21 were studied by direct standard dideoxy sequencing. Specific mutations were determined either by direct sequencing or by specific RFLP analysis. Cell lines were transfected with EGFR-mutant plasmids and analysed by western blot with antibodies specific for total or phosphorylated-EGFR.

Results

We found EGFR mutation in 12 of the 71 tumour samples (17%). One tumour contained two mutations. One mutation (p.R776G) was present as a germ line. Using an RFLP analysis, this mutation was not found in 954 alleles from healthy individuals studied, concluding that it is not a polymorphism. The mutation was not found either in genomic DNA from 912 lung cancer patients. Three additional EGFR germ-line mutations that were already described were not found in any of the studied samples. These observations show that EGFR mutated alleles are rare in the population. In vitro studies revealed that tyrosine autophosphorylation is enhanced in p.R776G-mutant EGFR when compared with wild-type EGFR. This enhanced autophosphorylation in the absence of ligand may be associated with a proliferative advantage.

Conclusions

Germ-line mutations in EGFR are rare but may contribute to oncogenesis
Development of modelling method selection tool for health services management: From problem structuring methods to modelling and simulation methods
Authors: Jun Gyuchan T , Morris Zoe , Eldabi Tillal , Harper Paul , Naseer Aisha , Patel Brijesh , Clarkson John P
Published: May 2011

Background

There is an increasing recognition that modelling and simulation can assist in the process of designing health care policies, strategies and operations. However, the current use is limited and answers to questions such as what methods to use and when remain somewhat underdeveloped.

Aim

The aim of this study is to provide a mechanism for decision makers in health services planning and management to compare a broad range of modelling and simulation methods so that they can better select and use them or better commission relevant modelling and simulation work.

Methods

This paper proposes a modelling and simulation method comparison and selection tool developed from a comprehensive literature review, the research team's extensive expertise and inputs from potential users. Twenty-eight different methods were identified, characterised by their relevance to different application areas, project life cycle stages, types of output and levels of insight, and four input resources required (time, money, knowledge and data).

Results

The characterisation is presented in matrix forms to allow quick comparison and selection. This paper also highlights significant knowledge gaps in the existing literature when assessing the applicability of particular approaches to health services management, where modelling and simulation skills are scarce let alone money and time.

Conclusions

A modelling and simulation method comparison and selection tool is developed to assist with the selection of methods appropriate to supporting specific decision making processes. In particular it addresses the issue of which method is most appropriate to which specific health services management problem, what the user might expect to be obtained from the method, and what is required to use the method. In summary, we believe the tool adds value to the scarce existing literature on methods comparison and selection.
Optimization of production of the anti-keratin 8 single-chain Fv TS1-218 in Pichia pastoris using design of experiments
Authors: Jafari Rozbeh , Sundström Birgitta E , Holm Patrik
Published: May 2011

Background

Optimization of conditions during recombinant protein production for improved yield is a major goal for protein scientists. Typically this is achieved by changing single crucial factor settings one at a time while other factors are kept fixed through trial-and-error experimentation. This approach may introduce larger bias and fail to identify interactions between the factors resulting in failure of finding the true optimal conditions.

Results

In this study we have utilized design of experiments in order to identify optimal culture conditions with the aim to improve the final yield of the anti-keratin 8 scFv TS1-218, during expression in P. pastoris in shake flasks. The effect of: pH, temperature and methanol concentration on the yield of TS1-218 using buffered minimal medium was investigated and a predictive model established. The results demonstrated that higher starting pH and lower temperatures during induction significantly increased the yield of TS1-218. Furthermore, the result demonstrated increased biomass accumulation and cell viability at lower temperatures which suggested that the higher yield of TS1-218 could be attributed to lower protease activity in the culture medium. The optimal conditions (pH 7.1, temperature 11°C and methanol concentration 1.2%) suggested by the predictive model yielded 21.4 mg TS1-218 which is a 21-fold improvement compared to the yield prior to optimization.

Conclusion

The results demonstrated that design of experiments can be utilized for a rapid optimization of initial culture conditions and that P. pastoris is highly capable of producing and secreting functional single-chain antibody fragments at temperatures as low as 11°C.
Serum 25-hydroxyvitamin D is inversely associated with body mass index in cancer
Authors: Vashi Pankaj G , Lammersfeld Carolyn A , Braun Donald P , Gupta Digant
Published: May 2011

Background

The association between vitamin D deficiency and obesity in healthy populations and different disease states remains unsettled with studies reporting conflicting findings. Moreover, current dietary recommendations for vitamin D do not take into account a person's body mass index (BMI). We investigated the relationship between serum 25-hydroxy-vitamin D [25(OH)D] and BMI in cancer.

Methods

A consecutive case series of 738 cancer patients. Serum 25(OH)D was measured at presentation to the hospital. The cohort was divided into 4 BMI groups (underweight: <18.5, normal weight: 18.5-24.9, overweight: 25-29.9, and obese: >30.0 kg/m2). Mean 25(OH)D was compared across the 4 BMI groups using ANOVA. Linear regression was used to quantify the relationship between BMI and 25(OH)D.

Results

303 were males and 435 females. Mean age at diagnosis was 55.6 years. The mean BMI was 27.9 kg/m2and mean serum 25(OH)D was 21.9 ng/ml. Most common cancers were lung (134), breast (131), colorectal (97), pancreas (86) and prostate (45). Obese patients had significantly lower serum 25(OH)D levels (17.9 ng/ml) as compared to normal weight (24.6 ng/ml) and overweight (22.8 ng/ml) patients; p < 0.001. After adjusting for age, every 1 kg/m2increase in BMI was significantly associated with 0.42 ng/ml decline in serum 25(OH)D levels.

Conclusions

Obese cancer patients (BMI >= 30 kg/m2) had significantly lower levels of serum 25(OH)D as compared to non-obese patients (BMI <30 kg/m2). BMI should be taken into account when assessing a patient's vitamin D status and more aggressive vitamin D supplementation should be considered in obese cancer patients.
Anti-inflammatory activity of edible oyster mushroom is mediated through the inhibition of NF-κB and AP-1 signaling
Authors: Jedinak Andrej , Dudhgaonkar Shailesh , Wu Qing-li , Simon James , Sliva Daniel
Published: May 2011

Background

Mushrooms are well recognized for their culinary properties as well as for their potency to enhance immune response. In the present study, we evaluated anti-inflammatory properties of an edible oyster mushroom (Pleurotus ostreatus) in vitro and in vivo.

Methods

RAW264.7 murine macrophage cell line and murine splenocytes were incubated with the oyster mushroom concentrate (OMC, 0-100 μg/ml) in the absence or presence of lipopolysacharide (LPS) or concanavalin A (ConA), respectively. Cell proliferation was determined by MTT assay. Expression of cytokines and proteins was measured by ELISA assay and Western blot analysis, respectively. DNA-binding activity was assayed by the gel-shift analysis. Inflammation in mice was induced by intraperitoneal injection of LPS.

Results

OMC suppressed LPS-induced secretion of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6), and IL-12p40 from RAW264.7 macrophages. OMC inhibited LPS-induced production of prostaglandin E2 (PGE2) and nitric oxide (NO) through the down-regulation of expression of COX-2 and iNOS, respectively. OMC also inhibited LPS-dependent DNA-binding activity of AP-1 and NF-κB in RAW264.7 cells. Oral administration of OMC markedly suppressed secretion of TNF-α and IL-6 in mice challenged with LPS in vivo. Anti-inflammatory activity of OMC was confirmed by the inhibition of proliferation and secretion of interferon-γ (IFN-γ), IL-2, and IL-6 from concanavalin A (ConA)-stimulated mouse splenocytes.

Conclusions

Our study suggests that oyster mushroom possesses anti-inflammatory activities and could be considered a dietary agent against inflammation. The health benefits of the oyster mushroom warrant further clinical studies.
Exposure to phthalates among premenstrual girls from rural and urban Gharbiah, Egypt: A pilot exposure assessment study
Authors: Colacino Justin A , Soliman Amr S , Calafat Antonia M , Nahar Muna S , Van Zomeren-Dohm Adrienne , Hablas Ahmed , Seifeldin Ibrahim A , Rozek Laura S , Dolinoy Dana C
Published: May 2011

Background

Phthalates have been identified as endocrine active compounds associated with developmental and reproductive toxicity. The exposure to phthalates in premenstrual Egyptian females remains unknown. The objective of this study was to characterize phthalate exposure of a potentially vulnerable population of premenstrual girls from urban and rural Egypt.

Materials and methods

We collected one spot urine sample from 60 10-13 year old females, 30 from rural Egypt, and 30 from urban Egypt from July to October 2009. Samples were analyzed for 11 phthalate metabolites. Additionally, we collected anthropometrics as well as questionnaire data concerning food storage behaviors, cooking practices, and cosmetic use. Phthalate metabolite concentrations were compared between urban and rural Egyptians as well as to age and gender matched Americans.

Results

Monoethyl phthalate (MEP), was detected at the highest concentration in urine of Egyptian girls (median: 43.2 ng/mL in rural, 98.8 ng/mL in urban). Concentrations of urinary metabolites of di-(2-ethylhexyl) phthalate and dibutyl phthalate were comparable between Egyptians and age matched US girls. Storage of food in plastic containers was a statistically significant predictor of urinary mono-isobutyl phthalate (MiBP) concentrations when comparing covariate adjusted means.

Conclusions

Urinary concentrations of phthalate metabolites were similar in Egyptian and US populations, suggesting that phthalate exposure also occurs in developing nations. Dietary intake is likely an important route of exposure to phthalates in both urban and rural populations.
Natriuretic Peptide Receptor A as a Novel Target for Prostate Cancer
Authors: Wang Xiaoqin , Raulji Payal , Mohapatra Shyam S , Patel Ronil , Hellermann Gary , Kong Xiaoyuan , Vera Pedro L , Meyer-Siegler Katherine L , Coppola Domenico , Mohapatra Subhra
Published: May 2011

Background

The receptor for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPRA), is expressed in cancer cells, and natriuretic peptides have been implicated in cancers. However, the direct role of NPRA signaling in prostate cancer remains unclear.

Results

NPRA expression was examined by western blotting, RT-PCR and immunohistochemistry. NPRA was downregulated by transfection of siRNA, shRNA and NPRA inhibitor (iNPRA). Antitumor efficacy of iNPRA was tested in mice using a TRAMP-C1 xenograft. Here, we demonstrated that NPRA is abundantly expressed on tumorigenic mouse and human prostate cells, but not in nontumorigenic prostate epithelial cells. NPRA expression showed positive correlation with clinical staging in a human PCa tissue microarray. Down-regulation of NPRA by siNPRA or iNPRA induced apoptosis in PCa cells. The mechanism of iNPRA-induced anti-PCa effects was linked to NPRA-induced expression of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine over-expressed in PCa and significantly reduced by siNPRA. Prostate tumor cells implanted in mice deficient in atrial natriuretic peptide receptor A (NPRA-KO) failed to grow, and treatment of TRAMP-C1 xenografts with iNPRA reduced tumor burden and MIF expression. Using the TRAMP spontaneous PCa model, we found that NPRA expression correlated with MIF expression during PCa progression.

Conclusions

Collectively, these results suggest that NPRA promotes PCa development in part by regulating MIF. Our findings also suggest that NPRA is a potential prognostic marker and a target for PCa therapy.
α-Linolenic acid prevents endoplasmic reticulum stress-mediated apoptosis of stearic acid lipotoxicity on primary rat hepatocytes
Authors: Zhang Yong , Dong Lei , Yang Xia , Shi Hongyang , Zhang Li
Published: May 2011

Aims

Lipid accumulation in non-adipose tissues leads to cell dysfunction and apoptosis, a phenomenon known as lipotoxicity. Unsaturated fatty acids may offset the lipotoxicity associated with saturated fatty acids. Stearic acid induced endoplasmic reticulum (ER) stress and caused apoptotic and necrotic cell death in the primary rat hepatocytes.

Methods

Cell viability was investigated using MTT assay, and apoptosis was evaluated with Hoechst 33342 staining. Western blot analysis was used to examine the changes in the expression levels of glucose regulated protein 78 (GRP78), glucose regulated protein 94 (GRP94), and C/EBP homologous protein (CHOP). Caspase-3 activity was evaluated using a Caspase-3 substrate kit.

Results

We have studied the ability of α-linolenic acid to prevent endoplasmic reticulum stress-mediated apoptosis of rat hepatocytes elicited by stearic acid and thapsigargin. Incubation of primary rat hepatocytes for 16 h with stearic acid produced a significant increase in cell death. Stearic acid also increased levels of three indicators of ER stress -- GRP78, CHOP, and GRP94. α-Linolenic acid distinctly reduced cell death and levels of all three indicators of ER stress brought about by stearic acid. Thapsigargin, which induces ER stress produced similar effects to those obtained using stearic acid; its effects were partly reversed by α-linolenic acid.

Conclusion

These results suggest that α-linolenic acid prevents ER stress-mediated apoptosis of stearic acid lipotoxicity on primary rat hepatocytes might become a target to develop new antiapoptotic compounds in nonalcoholic fatty liver disease (NAFLD).