bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic effect of preoperative serum estradiol level in postmenopausal breast cancer
Authors: Kim Ju-Yeon , Han Wonshik , Moon Hyeong-Gon , Ahn Soo Kyung , Kim Jisun , Lee Jun Woo , Kim Min Kyoon , Kim Taeryung , Noh Dong-Young
Published: October 2013

Background

The prognostic role of serum estrogen level in breast cancer patients is unclear. We investigated the prognostic importance of preoperative serum estradiol (E2) level in postmenopausal women according to their estrogen receptor (ER) status.

Methods

The medical records of 313 postmenopausal breast cancer patients who underwent surgery between 2006 and 2008 at a single institution were retrospectively evaluated. Patients who received neoadjuvant chemotherapy, synchronous bilateral breast cancer, or those with metastasis at diagnosis were excluded. Serum E2 and follicular stimulating hormone (FSH) levels were measured by radioimmunoassay and immunoradiometric assay, respectively, within 3 months prior to surgery. After a median follow-up of 52.0 months (11–77 months), 21 women were found to have metastatic disease.

Results

The overall, median E2 level was 13.0 pg/ml, and was slightly higher in ER-positive than ER-negative (p=0.69). The mean serum E2 level was significantly higher in patients with metastasis (17.41±8.34 pg/ml) than in those without metastasis (13.54±7.58 pg/ml) (p=0.02). Kaplan-Meier analysis using a cut-off of 13 pg/ml showed that, ER negative (p=0.02) but not ER positive (p>0.05) patients with higher E2 level showed significantly poorer metastasis-free survival. Multivariate analysis showed that, the high E2 level of ER negative tumors was an independent negative prognostic factor for metastasis- free survival (HR, 3.32; 95% CI, 1.05 to 10.51; p=0.04).

Conclusions

Higher preoperative serum E2 level had a negative prognostic effect in postmenopausal women with breast cancer, especially in the ER-negative subgroup.
Respective effects of phlebotomy losses and erythropoietin treatment on the need for blood transfusion in very premature infants
Authors: Becquet Odile , Guyot Delphine , Kuo Philippe , Pawlotsky Françoise , Besnard Marianne , Papouin Micheline , Lapillonne Alexandre
Published: October 2013

Background

The benefit to risk ratio of the treatment with erythropoietin (EPO) as a means of limiting the number of transfusions in very preterm infants during hospitalization, seems to be modest since the adoption of restrictive transfusion criteria and of policy limiting phlebotomy losses. We therefore aim to evaluate the factors associated with the number of late blood transfusion in very preterm infants in a unit where the routine use of EPO has been discontinued.

Methods

A comparative “before-after” study was carried out in premature infants born before 32 weeks postmenstrual age (PMA), over a period of one year before (EPO group) and one year after (non-EPO group) the discontinuation of EPO therapy.

Results

A total of 48 infants were included in the study (EPO=21; non-EPO=27). The number of infants transfused after the 15 day of life (D15) and the number of transfusions per infant after D15 were not significantly different between the two groups. In a multivariate analysis, the gestational age and the volume of blood drawn off during the first month of life significantly influenced the need for transfusions after the 15th day of life, independently of the treatment with EPO. The hemoglobin levels measured at different times of hospitalization (median postnatal age: 16, 33 and 67 days) were not significantly different between the two groups.

Conclusions

Our study shows that the discontinuation of EPO did not change the number of late transfusions. Even when a policy limiting phlebotomy losses is used, blood loss is an important and independent risk factor for late transfusion of very preterm infants.
Cross-sectional prevalence survey of intimate partner violence perpetration and victimization in Canadian military personnel
Authors: Zamorski Mark A , Wiens-Kinkaid Miriam E
Published: October 2013

Background

Intimate partner violence (IPV) is prevalent and is associated with a broad range of adverse consequences. In military organizations, IPV may have special implications, such as the potential of service-related mental disorders to trigger IPV. However, the Canadian Armed Forces (CAF) have limited data to guide their prevention and control efforts.

Methods

Self-reported IPV perpetration, victimization, and their correlates were assessed on a cross-sectional survey of a stratified random sample of currently-serving Canadian Regular Forces personnel (N = 2157). The four primary outcomes were perpetration or victimization of any physical and/or sexual or emotional and/or financial IPV over the lifespan of the current relationship.

Results

Among the 81% of the population in a current relationship, perpetration of any physical and/or sexual IPV was reported in 9%; victimization was reported in 15%. Any emotional and/or financial abuse was reported by 19% (perpetration) and 22% (victimization). Less physically injurious forms of abuse predominated. Logistic regression modelling showed that relationship dissatisfaction was independently associated with all four outcomes (OR range = 2.3 to 3.7). Probable depression was associated with all outcomes except physical and/or sexual IPV victimization (OR range = 2.5 – 2.7). PTSD symptoms were only associated with physical and/or sexual IPV perpetration (OR = 3.2, CI = 1.4 to 7.9). High-risk drinking was associated with emotional and/or financial abuse. Risk of IPV was lowest in those who had recent deployment experience; remote deployment experience (vs. never having deployed) was an independent risk factor for all IPV outcomes (OR range = 2.0 – 3.4).

Conclusions

IPV affects an important minority of military families; less severe cases predominate. Mental disorders, high-risk drinking, relationship dissatisfaction, and remote deployment were independently associated with abuse outcomes. The primary limitations of this analysis are its use of self-report data from military personnel (not their intimate partners) and the cross-sectional nature of the survey. Prevention efforts in the CAF need to target the full spectrum of IPV. Mental disorders, high-risk drinking, and relationship dissatisfaction are potential targets for risk reduction. Additional research is needed to understand the association of remote deployment with IPV.
Meta-analysis of the association of HLA-DRB1 with rheumatoid arthritis in Chinese populations
Authors: Yang Meng , Kuang Xiaocong , Li Jianmin , Pan Yanbin , Tan Meile , Lu Binzhu , Cheng Qiumei , Wu Lingyan , Pang Guodong
Published: October 2013

Background

Individual studies have reported different results regarding the association of HLA alleles with RA in Chinese populations. This study was performed to systematically summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in China.

Methods

We examined the case–control studies concerned about the relationship between HLA-DRB1and RA and differences of clinical and laboratory parameters between the HLA-DR4 (DR4)+ and DR4- in RA patients in Chinese populations. Odds ratios (ORs) and weighted mean difference (WMD) with corresponding 95% confidence intervals (CI) was used to describe the relationship.

Results

22 studies with 1690 cases and 1793 controls were included. Chinese populations with RA had significantly higher frequencies of HLA-DRB1*04, *0401, *0404, *0405 and *0410 than controls (ORDRB1*04 =4.19, 95% CI =3.44–5.11, p<0.00001; ORDRB1*0401 =2.53, 95% CI =1.54–4.16, p=0.0003; ORDRB1*0404 =2.28, 95% CI =1.28–4.06, p=0.005; ORDRB1*0405=3.71, 95% CI =2.52–5.45, p<0.00001; ORDRB1*0410 =2.99, 95% CI =1.25–7.14, p=0.01respectively). As to laboratory parameters, Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid factor (RF), Anti-cyclic citrullinated peptide antibodies (Anti-CCP ) in patients with DR4+ were higher than patients with DR4- (WMD=0.26, 95% CI =0.15–0.37, p<0.00001; WMD = 0.26, 95% CI =0.12–0.41, p=0.0005; WMD = 0.44, 95% CI =0.23–0.65, p<0.00001; WMD = 0.58, 95% CI =0.24–0.91, p=0.0007 respectively). As to clinical features, there was no difference in duration of morning stiffness, number of swollen joints, number of joint tenderness, X-ray phases and joint function between the DR4+ and DR4- in RA patients.

Conclusions

It was found that HLA-DRB1*04, *0401, *0404, *0405 and *0410 are risk factors for RA in Chinese populations. ESR, CRP, RF, Anti-CCP are different between the DR4+ and DR4- in RA patients in Chinese populations, while there’s no difference for indexes of clinical features.
Autonomic care platform for optimizing query performance
Authors: Steurbaut Kristof , Latré Steven , Decruyenaere Johan , Turck Filip De
Published: October 2013

Background

As the amount of information in electronic health care systems increases, data operations get more complicated and time-consuming. Intensive Care platforms require a timely processing of data retrievals to guarantee the continuous display of recent data of patients. Physicians and nurses rely on this data for their decision making. Manual optimization of query executions has become difficult to handle due to the increased amount of queries across multiple sources. Hence, a more automated management is necessary to increase the performance of database queries. The autonomic computing paradigm promises an approach in which the system adapts itself and acts as self-managing entity, thereby limiting human interventions and taking actions. Despite the usage of autonomic control loops in network and software systems, this approach has not been applied so far for health information systems.

Methods

We extend the COSARA architecture, an infection surveillance and antibiotic management service platform for the Intensive Care Unit (ICU), with self-managed components to increase the performance of data retrievals. We used real-life ICU COSARA queries to analyse slow performance and measure the impact of optimizations. Each day more than 2 million COSARA queries are executed. Three control loops, which monitor the executions and take action, have been proposed: reactive, deliberative and reflective control loops. We focus on improvements of the execution time of microbiology queries directly related to the visual displays of patients’ data on the bedside screens.

Results

The results show that autonomic control loops are beneficial for the optimizations in the data executions in the ICU. The application of reactive control loop results in a reduction of 8.61% of the average execution time of microbiology results. The combined application of the reactive and deliberative control loop results in an average query time reduction of 10.92% and the combination of reactive, deliberative and reflective control loops provides a reduction of 13.04%.

Conclusions

We found that by controlled reduction of queries’ executions the performance for the end-user can be improved. The implementation of autonomic control loops in an existing health platform, COSARA, has a positive effect on the timely data visualization for the physician and nurse.
Malaria control in South Sudan, 2006–2013: strategies, progress and challenges
Authors: Pasquale Harriet , Jarvese Martina , Julla Ahmed , Doggale Constantino , Sebit Bakhit , Lual Mark Y , Baba Samson P , Chanda Emmanuel
Published: October 2013

Background

South Sudan has borne the brunt of years of chronic warfare and probably has the highest malaria burden in sub-Saharan Africa. However, effective malaria control in post-conflict settings is hampered by a multiplicity of challenges. This manuscript reports on the strategies, progress and challenges of malaria control in South Sudan and serves as an example epitome for programmes operating in similar environments and provides a window for leveraging resources.

Case description

To evaluate progress and challenges of the national malaria control programme an in-depth appraisal was undertaken according to the World Health Organization standard procedures for malaria programme performance review. Methodical analysis of published and unpublished documents on malaria control in South Sudan was conducted. To ensure completeness, findings of internal thematic desk assessments were triangulated in the field and updated by external review teams.

Discussion and evaluation

South Sudan has strived to make progress in implementing the WHO recommended malaria control interventions as set out in the 2006–2013 National Malaria Strategic Plan. The country has faced enormous programmatic constraints including infrastructure, human and financial resource and a weak health system compounded by an increasing number of refugees, returnees and internally displaced people. The findings present a platform on which to tailor an evidence-based 2014–2018 national malaria strategic plan for the country and a unique opportunity for providing a model for countries in a post-conflict situation.

Conclusions

The prospects for effective malaria control and elimination are huge in South Sudan. Nevertheless, strengthened coordination, infrastructure and human resource capacity, monitoring and evaluation are required. To achieve all this, allocation of adequate local funding would be critical.
Serum retinol binding protein 4 is negatively related to beta cell function in Chinese women with non-alcoholic fatty liver disease: a cross-sectional study
Authors: Yan Hongmei , Chang Xinxia , Xia Mingfeng , Bian Hua , Zhang Linshan , Lin Huandong , Chen Gang , Zeng Mengsu , Gao Xin
Published: October 2013

Background

To observe the relationship between serum retinol binding protein 4(RBP4) and β cell function in Chinese subjects with non-alcoholic fatty liver disease (NAFLD) and without known diabetes.

Methods

106 patients diagnosed as fatty liver by ultrasonography (M/F: 61/45; aged 47.44 ± 14.16 years) were enrolled in our current cross-sectional study. Subjects with known diabetes, chronic virus hepatitis and excessive alcohol consumption were excluded. Serum RBP4 was detected by ELISA and validated by quantitative Western blotting. β cell function were assessed by HOMA in all subjects and by hyperglycemic clamp in 17 normal glucose tolerance subjects (M = 6, F = 11).

Results

The levels of serum RBP4 in men were higher than that in women (55.96 ± 11.14 vs 45.87 ± 10.31 μg/ml, p < 0.001). Pearson’s correlation analysis demonstrated that in women, serum RBP4 levels were significantly associated with fasting blood glucose (FBG), HOMA-β, and increment of first phase insulin secretion (1PH), but not associated with age, BMI, waist circumference, WHR, systolic (SBP) and diastolic blood pressure (DBP), TC, TG, HDL-c, LDL-c, 2 h blood glucose, HOMA-IR, ALT, AST, γ-GT, hepatic fat content (HFC), and insulin sensitivity index (ISI). However, in men, serum RBP4 levels were significantly associated with HDL-c, ALT, AST, but not associated with any other parameters as mentioned above. A stepwise multiple linear regression analysis demonstrated that in women, HOMA-IR and RBP4 were significantly associated with HOMA-β, while in men, HOMA-IR and BMI were significantly variables associated with HOMA-β.

Conclusions

Serum RBP4, secreted mainly by liver and adipose tissue, may involve in the pathogenesis of β cell dysfunction in Chinese women patients with NAFLD.
Astrocytes acquire resistance to iron-dependent oxidative stress upon proinflammatory activation
Authors: Macco Romina , Pelizzoni Ilaria , Consonni Alessandra , Vitali Ilaria , Giacalone Giacomo , Martinelli Boneschi Filippo , Codazzi Franca , Grohovaz Fabio , Zacchetti Daniele
Published: October 2013

Background

Astrocytes respond to local insults within the brain and the spinal cord with important changes in their phenotype. This process, overall known as “activation”, is observed upon proinflammatory stimulation and leads astrocytes to acquire either a detrimental phenotype, thereby contributing to the neurodegenerative process, or a protective phenotype, thus supporting neuronal survival. Within the mechanisms responsible for inflammatory neurodegeneration, oxidative stress plays a major role and has recently been recognized to be heavily influenced by changes in cytosolic iron levels. In this work, we investigated how activation affects the competence of astrocytes to handle iron overload and the ensuing oxidative stress.

Methods

Cultures of pure cortical astrocytes were preincubated with proinflammatory cytokines (interleukin-1β and tumor necrosis factor α) or conditioned medium from lipopolysaccharide-activated microglia to promote activation and then exposed to a protocol of iron overload.

Results

We demonstrate that activated astrocytes display an efficient protection against iron-mediated oxidative stress and cell death. Based on this evidence, we performed a comprehensive biochemical and molecular analysis, including a transcriptomic approach, to identify the molecular basis of this resistance.

Conclusions

We propose the protective phenotype acquired after activation not to involve the most common astrocytic antioxidant pathway, based on the Nrf2 transcription factor, but to result from a complex change in the expression and activity of several genes involved in the control of cellular redox state.
In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis
Authors: Watkins Richard L , Zou Wei , Denton Paul W , Krisko John F , Foster John L , Garcia J Victor
Published: October 2013

Background

The HIV-1 accessory protein, Nef, is decisive for progression to AIDS. In vitro characterization of the protein has described many Nef activities of unknown in vivo significance including CD4 downregulation and a number of activities that depend on Nef interacting with host SH3 domain proteins. Here, we use the BLT humanized mouse model of HIV-1 infection to assess their impact on viral replication and pathogenesis and the selection pressure to restore these activities using enforced in vivo evolution.

Results

We followed the evolution of HIV-1LAI (LAI) with a frame-shifted nef (LAINeffs) during infection of BLT mice. LAINeffs was rapidly replaced in blood by virus with short deletions in nef that restored the open reading frame (LAINeffs∆-1 and LAINeffs∆-13). Subsequently, LAINeffs∆-1 was often replaced by wild type LAI. Unexpectedly, LAINeffs∆-1 and LAINeffs∆-13 Nefs were specifically defective for CD4 downregulation activity. Viruses with these mutant nefs were used to infect BLT mice. LAINeffs∆-1 and LAINeffs∆-13 exhibited three-fold reduced viral replication (compared to LAI) and a 50% reduction of systemic CD4+ T cells (>90% for LAI) demonstrating the importance of CD4 downregulation. These results also demonstrate that functions other than CD4 downregulation enhanced viral replication and pathogenesis of LAINeffs∆-1 and LAINeffs∆-13 compared to LAINeffs. To gain insight into the nature of these activities, we constructed the double mutant P72A/P75A. Multiple Nef activities can be negated by mutating the SH3 domain binding site (P72Q73V74P75L76R77) to P72A/P75A and this mutation does not affect CD4 downregulation. Virus with nef mutated to P72A/P75A closely resembled the wild-type virus in vivo as viral replication and pathogenesis was not significantly altered. Unlike LAINeffs described above, the P72A/P75A mutation had a very weak tendency to revert to wild type sequence.

Conclusions

The in vivo phenotype of Nef is significantly dependent on CD4 downregulation but minimally on the numerous Nef activities that require an intact SH3 domain binding motif. These results suggest that CD4 downregulation plus one or more unknown Nef activities contribute to enhanced viral replication and pathogenesis and are suitable targets for anti-HIV therapy. Enforced evolution studies in BLT mice will greatly facilitate identification of these critical activities.
Bluetongue virus infection induces aberrant mitosis in mammalian cells
Authors: Shaw Andrew E , Brüning-Richardson Anke , Morrison Ewan E , Bond Jacquelyn , Simpson Jennifer , Ross-Smith Natalie , Alpar Oya , Mertens Peter PC , Monaghan Paul
Published: October 2013

Background

Bluetongue virus (BTV) is an arbovirus that is responsible for ‘bluetongue’, an economically important disease of livestock. Although BTV is well characterised at the protein level, less is known regarding its interaction with host cells. During studies of virus inclusion body formation we observed what appeared to be a large proportion of cells in mitosis. Although the modulation of the cell cycle is well established for many viruses, this was a novel observation for BTV. We therefore undertook a study to reveal in more depth the impact of BTV upon cell division.

Methods

We used a confocal microscopy approach to investigate the localisation of BTV proteins in a cellular context with their respective position relative to cellular proteins. In addition, to quantitatively assess the frequency of aberrant mitosis induction by the viral non-structural protein (NS) 2 we utilised live cell imaging to monitor HeLa-mCherry tubulin cells transfected with a plasmid expressing NS2.

Results

Our data showed that these ‘aberrant mitoses’ can be induced in multiple cell types and by different strains of BTV. Further study confirmed multiplication of the centrosomes, each resulting in a separate mitotic spindle during mitosis. Interestingly, the BTV NS1 protein was strongly localised to the centrosomal regions. In a separate, yet related observation, the BTV NS2 protein was co-localised with the condensed chromosomes to a region suggestive of the kinetochore. Live cell imaging revealed that expression of an EGFP-NS2 fusion protein in HeLa-mCherry tubulin cells also results in mitotic defects.

Conclusions

We hypothesise that NS2 is a microtubule cargo protein that may inadvertently disrupt the interaction of microtubule tips with the kinetochores during mitosis. Furthermore, the BTV NS1 protein was distinctly localised to a region encompassing the centrosome and may therefore be, at least in part, responsible for the disruption of the centrosome as observed in BTV infected mammalian cells.
Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters
Authors: Jung Jinhong , Yoon Sang Min , Kim So Yeon , Cho Byungchul , Park Jin-hong , Kim Su Ssan , Song Si Yeol , Lee Sang-wook , Ahn Seung Do , Choi Eun Kyung , Kim Jong Hoon
Published: October 2013

Background

To investigate the clinical and dose–volumetric parameters that predict the risk of radiation-induced liver disease (RILD) for patients with small, unresectable hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).

Methods

Between March 2007 and December 2009, 92 patients with HCC treated with SBRT were reviewed for RILD within 3 months of completing treatment. RILD was evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. A dose of 10–20 Gy (median, 15 Gy) per fraction was given over 3–4 consecutive days for a total dose of 30–60 Gy (median, 45 Gy). The following clinical and dose–volumetric parameters were examined: age, gender, Child-Pugh class, presence of hepatitis B virus, gross tumor volume, normal liver volume, radiation dose, fraction size, mean dose to the normal liver, and normal liver volumes receiving from < 5 Gy to < 60 Gy (in increments of 5 Gy).

Results

Seventeen (18.5%) of the 92 patients developed grade 2 or worse RILD after SBRT (49 patients in grade 1, 11 in grade 2, and 6 in ≥ grade 3). On univariate analysis, Child-Pugh class was identified as a significant clinical parameter, while normal liver volume and normal liver volumes receiving from < 15 Gy to < 60 Gy were the significant dose–volumetric parameters. Upon multivariate analysis, only Child-Pugh class was a significant parameter for predicting grade 2 or worse RILD.

Conclusions

The Child-Pugh B cirrhosis was found to have a significantly greater susceptibility to the development of grade 2 or worse RILD after SBRT in patients with small, unresectable HCC. Additional efforts aimed at testing other models to predict the risk of RILD in a large series of HCC patients treated with SBRT are needed.
Histone deacetylase-3 interacts with ataxin-7 and is altered in a spinocerebellar ataxia type 7 mouse model
Authors: Duncan Carlotta E , An Mahru C , Papanikolaou Theodora , Rugani Caitlin , Vitelli Cathy , Ellerby Lisa M
Published: October 2013

Spinocerebellar ataxia type 7 (SCA7) is caused by a toxic polyglutamine (polyQ) expansion in the N-terminus of the protein ataxin-7. Ataxin-7 has a known function in the histone acetylase complex, Spt/Ada/Gcn5 acetylase (STAGA) chromatin-remodeling complex. We hypothesized that some histone deacetylase (HDAC) family members would impact the posttranslational modification of normal and expanded ataxin-7 and possibly modulate ataxin-7 function or neurotoxicity associated with the polyQ expansion. Interestingly, when we coexpressed each HDAC family member in the presence of ataxin-7 we found that HDAC3 increased the posttranslational modification of normal and expanded ataxin-7. Specifically, HDAC3 stabilized ataxin-7 and increased modification of the protein. Further, HDAC3 physically interacts with ataxin-7. The physical interaction of HDAC3 with normal and polyQ-expanded ataxin-7 affects the toxicity in a polyQ-dependent manner. We detect robust HDAC3 expression in neurons and glia in the cerebellum and an increase in the levels of HDAC3 in SCA7 mice. Consistent with this we found altered lysine acetylation levels and deacetylase activity in the brains of SCA7 transgenic mice. This study implicates HDAC3 and ataxin-7 interaction as a target for therapeutic intervention in SCA7, adding to a growing list of neurodegenerative diseases that may be treated by HDAC inhibitors.
Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries
Authors: Lee Yi-Ying , Hsu Chih-Yuan , Lin Ling-Jiun , Chang Chih-Chun , Cheng Hsiao-Chun , Yeh Tsung-Hsien , Hu Rei-Hsing , Lin Che , Xie Zhen , Chen Bor-Sen
Published: October 2013

Background

Synthetic genetic transistors are vital for signal amplification and switching in genetic circuits. However, it is still problematic to efficiently select the adequate promoters, Ribosome Binding Sides (RBSs) and inducer concentrations to construct a genetic transistor with the desired linear amplification or switching in the Input/Output (I/O) characteristics for practical applications.

Results

Three kinds of promoter-RBS libraries, i.e., a constitutive promoter-RBS library, a repressor-regulated promoter-RBS library and an activator-regulated promoter-RBS library, are constructed for systematic genetic circuit design using the identified kinetic strengths of their promoter-RBS components.

According to the dynamic model of genetic transistors, a design methodology for genetic transistors via a Genetic Algorithm (GA)-based searching algorithm is developed to search for a set of promoter-RBS components and adequate concentrations of inducers to achieve the prescribed I/O characteristics of a genetic transistor. Furthermore, according to design specifications for different types of genetic transistors, a look-up table is built for genetic transistor design, from which we could easily select an adequate set of promoter-RBS components and adequate concentrations of external inducers for a specific genetic transistor.

Conclusion

This systematic design method will reduce the time spent using trial-and-error methods in the experimental procedure for a genetic transistor with a desired I/O characteristic. We demonstrate the applicability of our design methodology to genetic transistors that have desirable linear amplification or switching by employing promoter-RBS library searching.
A school based study of psychological disturbance in children following the Omagh bomb
Authors: McDermott Maura , Duffy Michael , Percy Andy , Fitzgerald Michael , Cole Claire
Published: October 2013

Objective

To assess the extent and nature of psychiatric morbidity among children (aged 8 to 13 years) 15 months after a car bomb explosion in the town of Omagh, Northern Ireland.

Method

A survey was conducted of 1945 school children attending 13 schools in the Omagh district. Questionnaires included demographic details, measures of exposure, the Horowitz Impact of Events Scale, the Birleson Self-Rating Depression Scale, and the Spence Children’s Anxiety Scale.

Results

Children directly exposed to the bomb reported higher levels of probable PTSD (70%), and psychological distress than those not exposed. Direct exposure was more closely associated with an increase in PTSD symptoms than in general psychiatric distress. Significant predictors of increased IES scores included being male, witnessing people injured and reporting a perceived life threat but when co-morbid anxiety and depression are included as potential predictors anxiety remains the only significant predictor of PTSD scores.

Conclusions

School-based studies are a potentially valuable means of screening and assessing for PTSD in children after large-scale tragedies. Assessment should consider type of exposure, perceived life threat and other co-morbid anxiety as risk factors for PTSD.
Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges
Authors: Wopereis Suzan , Wolvers Danielle , van Erk Marjan , Gribnau Michiel , Kremer Bas , van Dorsten Ferdi A , Boelsma Esther , Garczarek Ursula , Cnubben Nicole , Frenken Leon , van der Logt Paul , Hendriks Henk FJ , Albers Ruud , van Duynhoven John , van Ommen Ben , Jacobs Doris M
Published: October 2013

Background

Resilience or the ability of our body to cope with daily-life challenges has been proposed as a new definition of health, with restoration of homeostasis as target resultant of various physiological stress responses. Challenge models may thus be a sensitive measure to study the body’s health. The objective of this study was to select a dietary challenge model for the assessment of inflammatory resilience. Meals are a challenge to metabolic homeostasis and are suggested to affect inflammatory pathways, yet data in literature are limited and inconsistent.

Method

The kinetic responses of three different dietary challenges and a water control challenge were assessed on various metabolic and inflammatory markers in 14 healthy males and females using a full cross-over study design. The dietary challenges included glucose (75 g glucose in 300 ml water), lipids (200 ml whipping cream) and a mix of glucose and lipids (same amounts as above), respectively. Blood samples were collected at baseline and at 0.5, 1, 2, 4, 6, 8 and 10 h after consumption of the treatment products. Inflammation (IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α CRP, ICAM-1, VCAM-1, SAA, E-selectin, P-selectin, thrombomodulin, leukocytes, neutrophils, lymphocytes) and clinical (e.g. glucose, insulin, triglycerides) markers as well as gene expression in blood cells and plasma oxylipin profiles were measured.

Results

All three dietary challenges induced changes related to metabolic control such as increases in glucose and insulin after the glucose challenge and increases in triglycerides after the lipid challenge. In addition, differences between the challenges were observed for precursor oxylipins and some downstream metabolites including DiHETrE’s and HODE’s. However, none of the dietary challenges induced an acute inflammatory response, except for a modest increase in circulating leukocyte numbers after the glucose and mix challenges. Furthermore, subtle, yet statistically significant increases in vascular inflammatory markers (sICAM-1 and sVCAM-1) were found after the mix challenge, when compared to the water control challenge.

Conclusions

This study shows that dietary glucose and lipid challenges did not induce a strong acute inflammatory response in healthy subjects, as quantified by an accurate and broad panel of parameters.
Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma
Authors: Huang Jiayuan , Song Haizhu , Liu Biao , Yu Bo , Wang Rui , Chen Longbang
Published: October 2013

Background

According to the International Multidisciplinary Classification of Lung Adenocarcinoma (LAD) by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) in 2011, the diagnosis of LAD is changing from simple morphology into a comprehensive multidisciplinary classification. The aim of this study is to detect the expression of Notch-1 and analyze its clinicopathological or prognostic significance in different histological subtypes of Lung Adenocarcinomas (LADs).

Methods

Western blot and Semi-quantitative Reverse transcription-polymerase chain reaction (RT-PCR) assays, as well as immunohisitochemistry, were performed to detect the expression of Notch-1 in LAD cells and tissue samples. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the correlation of Notch-1 expression with clinicopathological factors and prognosis of LAD patients.

Results

The expression level of Notch-1 protein in LAD cell lines or tissues was significantly lower than that in normal human bronchial epithelial cell line (16HBE) or nontumor tissues (P < 0.05). By statistical analyses, it was observed that negative Notch-1 expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.026) in LAD patients. Also, the recurrence rate of Notch-1-positive group was higher than the Notch-1-negative group (P = 0.001), and patients with positive Notch-1 expression have a prolonged progression of overall survival (P = 0.033). More interestingly, the expression of Notch-1 protein was often observed to be negative in solid predominant adenocarcinoma (SPA) tissues, but highly expressed in papillary predominant adenocarcinoma (PPA) and micropapillary predominant adenocarcinoma (MPA) tissues. Kaplan-Meier survival analysis showed that patients with positive Notch-1 expression had a prolonged progression of overall survival compared with those with negative Notch-1 expression (P = 0.033). The median survival time of Notch-1-positive or negative patients was 64.6 months (95% CI: 31.497-97.703 months) or 36.0 months (95% CI: 12.132-59.868 months).

Conclusions

Notch-1 could be used as a predictable biomarker to be detected in different pathological and histological subtypes in LAD for diagnosis or prognosis.
Effects of therapeutic goal management (TGM) on treatment attendance and drug abstinence among men with co-occurring substance use and axis I mental disorders who are homeless: results of the Birmingham EARTH program
Authors: Davidson Anna , Jensen Michael , Burgess Emilee , Stevens Angee , Hayes Lauren , Sieweke Susan , Stough Karen , Wright Anne , McCarty Robin , Eddleman Lillian , Kim Young-il , Milby Jesse B , Schumacher Joseph E
Published: October 2013

Purpose

This study describes the implementation and impact of Therapeutic Goal Management (TGM) in a Substance Abuse and Mental Health Services Administration (SAMHSA)-sponsored demonstration project entitled Enhanced Addiction Recovery through Housing (EARTH).

Participants

The sample included 28 male participants followed at six months who completed some treatment. Forty-three percent were Caucasian, and 57% were African American. The average age of participants was 42 years.

Design

The relationships between TGM goal achievement, treatment attendance, and drug abstinence outcomes were studied among EARTH program participants who were homeless and met criteria for co-occurring substance use and severe DSM-IV Axis I mental disorders.

Results

The results revealed an overall drug abstinence rate of 72.4% over six months and significant positive relationships between TGM goal achievement and drug abstinence (r = 0.693) and TGM goal achievement and treatment attendance (r = 0.843).

Conclusions

This research demonstrated the relationship and potential positive impact of systematically setting, monitoring, and reinforcing personalized goals in multiple life areas on drug abstinence and treatment attendance outcomes among persons who are homeless with co-occurring substance use and other Axis I disorders in a integrated community service delivery program.
Gene expression analysis in allergology: the prediction of Hymenoptera venom allergy severity and treatment efficacy
Authors: Niedoszytko Marek , Gruchała‐Niedoszytko Marta , Jassem Ewa
Published: October 2013

Insect venom allergy (IVA) may result in the most severe systemic reactions seen in allergology. The only potentially curative treatment option is venom immunotherapy (VIT) over 3 to 5 years. This treatment is effective in more than 90% of subjects but no reliable predictors of VIT effectiveness exist. Sting challenge with a living insect can be performed to assess the effectiveness of VIT: the predictive value of sting challenge can be highly sensitive in patients with honeybee venom allergy whereas in yellow jacket allergy, a negative result can be reliable if the challenge has been repeated at least 3 times.

The analysis of gene expression may be a step towards personalized venom immunotherapy assessing the effectiveness of treatment, the minimal required time for VIT and the persistence of long term tolerance induced by the treatment. Recent studies have enabled construction of a predictive model that could potentially be used in clinical practice to assess the efficacy of insect venom immunotherapy. A set of 69 genes that may be responsible for long‐term protection was identified. Further analysis of the previously identified 6 transcripts make up the 18 gene predictive peripheral blood showed differences in patients treated with IVA. Further studies are needed to investigate the usefulness of gene expression analysis and other markers in the prediction of VIT effectiveness.
Development and validation of RP-HPLC-PDA method for the quantification of eugenol in developed nanoemulsion gel and nanoparticles
Authors: Pramod Kannissery , Ilyas Ura Kottil , Kamal Yoonuskunju Thajudeenkoya , Ahmad Sayeed , Ansari Shahid Hussain , Ali Javed
Published: October 2013

Background

Eugenol is a potent phytochemical, and a plethora of delivery systems for this bioactive agent is being developed. Reversed-phase high-pressure liquid chromatography equipped with photodiode array detector (RP-HPLC-PDA) method is very useful in the quantification of the phytochemicals.

Methods

The RP-HPLC-PDA system with C18 reversed-phase column (250???4.6?mm, particle size 5??m) was used in this study. Acetonitrile and water in 1:1 (v/v) ratio was chosen as the mobile phase under a column temperature of 25?C. The detection wavelength was set at 280?nm with a flow rate of 1?mL/min. Method validation was performed according to the International Conference on Harmonization guidelines.

Results

HPLC method for the quantification of eugenol was successfully developed and validated. The method was validated in terms of linearity and range, accuracy, precision, specificity, robustness, detection limit, and quantitation limit.

Conclusions

The developed RP-HPLC-PDA could be successfully employed for the quantification of eugenol in nanoemulsion gel and nanoparticles.
A Selective TSH Receptor Antagonist Inhibits Stimulation of Thyroid Function in Female Mice
Authors: Neumann Susanne , Nir Eshel A. , Eliseeva Elena , Huang Wenwei , Marugan Juan , Xiao Jingbo , Dulcey Andrés E. , Gershengorn Marvin C.
Published: October 2013

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.
The N-Chlorination of Primary Amines Using FeCl3 and m-CPBA
Authors: Liu Jia , Xu Junchao , Ren Jiangmeng , Zeng Bu-Bing
Published: October 2013

A simple and effective method for the synthesis of N,N-dichloroamines from primary amines was conducted successfully with m-CPBA as oxidant and FeCl3 as chlorine source at 0 °C. Moreover, N,N-dichloroamines could be converted into nitriles or N-chloroimines in good yields.
Don't Ask Me If You Will Not Listen: The Dilemma of Consultative Participation
Authors: Corgnet Brice , Hernán González Roberto
Published: October 2013

We study the effect of consultative participation in an experimental principal–agent game, where the principal can consult the agent's preferred option regarding the cost function of the transfer to be implemented in the final stage of the game. We show that consulting the agent was beneficial to principals as long as they followed the agent's choice. Ignoring the agent's choice was detrimental to the principal because it engendered negative emotions and low levels of transfers. Nevertheless, the majority of principals were reluctant to change their mind and adopt the agent's proposal. Our results suggest that the ability to change one's own mind is an important dimension of managerial success.

Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2013.1786 .

This paper was accepted by Teck-Hua Ho, behavioral economics.
Verse and Prose in the Continuations of Chrétien de Troyes’ Conte du Graal
Authors: Gaggero Massimiliano
Published: October 2013

The aim of this article is to study the Third and Fourth Continuations’ reaction to the interlaced structure of their prose intertexts, the Haut livre du Graal and the Lancelot en prose . A detailed comparison shows that, although the verse texts have borrowed episodes from the prose texts, these have been recast according to a narrative strategy inherited from the First and the Second Continuation, which is typical of the verse tradition.
The Communication of Culture: Speech and the ‘Grail’ Procession in Historia Peredur vab Efrawc
Authors: McMullen A. Joseph
Published: October 2013

This article focuses on the emphasis on speech in Peredur as integral to the tale’s narrative structure and as pointing outside of the text to the socio-cultural climate of medieval Wales. Peredur must learn how to communicate culture—how to transfer Welsh culture through language—a lesson with significant implications for text’s audience.
Jessie Weston and the Green Knight
Authors: Nastali Daniel
Published: October 2013

Although Sir Gawain and the Green Knight was first printed in 1839, it drew little attention from the reading public until the early twentieth century. Today it is the most familiar of the romances, with manifestations ranging from new translations to films, novels, and comics. This article traces the story’s journey from the province of early Arthurian scholarship to comtemporary popular culture.
King Arthur and His Knights for Edwardian Children
Authors: Richmond Velma Bourgeois
Published: October 2013

Arthurian stories were retold for Edwardian children in a variety of collections, single texts, and school readers. This essay considers samples, from extravagant books to modest pamphlets, identifying favored characters and episodes in order to describe how skilled writers and illustrators created influential Arthurian children’s literature.
Envisioning the End: History and Consciousness in Medieval English Arthurian Romance
Authors: Whitman Jon
Published: October 2013

The evocation of historical consciousness in English Arthurian romance suggests deep changes in attitude toward temporal experience in the late Middle Ages.
Henry Cumming—Vladimir Nabokov’s First Drawing Master
Authors: Shapiro Gavriel
Published: October 2013

The article discusses Henry Cumming’s impact on Nabokov’s artistic development. It shows that, although not a distinguished painter, Cumming was a gifted pedagogue. He instructed Nabokov the boy into the basic laws and rules of draftsmanship and inculcated in his young charge an early fascination with and emotional attachment to painting. When Nabokov turned from the brush to the quill, he did not forget his lessons with Cumming and channeled his penchant for painting, specifically landscape, into his fiction.
Recourse to Eden: Tracing the Roots of Nabokov’s Adamic Themes
Authors: Link Christopher A.
Published: October 2013

This essay examines both the breadth and the depth of Nabokov's engagement with the biblical myth of Eden and its many resonant, interrelated themes: divine creation, Adamic man, paradisal love, diabolic temptation, exile and loss, the persistence of memory, and the desire to regain—either in this world or the next—one form or another of Edenic bliss. While focusing principally on the "roots" of Nabokov's Adamic and Edenic themes as they appear in several early poems and short stories, in the autobiography, Speak, Memory , and in his first novel, Mary , this essay also argues more broadly that the biblical myth of a lost paradise (and the subsequent echoes of this biblical tradition in later representational art and literature) continued to influence and inform Nabokov's writings significantly throughout his entire career, particularly in such later masterworks as Lolita and Ada . Since the author regularly dismissed all claims of "influence" upon his works, this essay aims chiefly at establishing and exploring, with fresh appreciation, Nabokov's substantial understanding of, and sustained intertextual reliance upon, biblical narrative and the extended tradition (Dante, Milton, Marvell, etc.) of Edenic paradise and Adamic fall.
Lolita and Transatlantic Family Structures
Authors: McGehee Michael
Published: October 2013

This essay examines how contrasting family configurations play into the repression, development, and expression of Humbert Humbert's pedophiliac desires in Nabokov's Lolita . Drawing upon Alexis de Tocqueville's distinctions between the hierarchical families of France and the comparatively egalitarian families of the United States, the essay advances three interrelated claims: first, the traditional European family's rigid boundaries, supported by patriarchy and economic interest, keep nymphets inaccessible to Humbert as long as he lives in France; second, Humbert is able to carry out his desires for nymphets only in America, where the egalitarian family allows for the parent-child antagonism that isolates Lolita from her mother and makes her sexually available to her adult pursuer; third, to protect and prolong his relationship with Lolita, Humbert works to implement in America his own reconstruction of the traditional European family, an attempt finally doomed by the strength of his passion for the nymphet. These lines of argument together suggest that the development of plot and character in Nabokov's novel depends in large part on his representation of family structures on both sides of the Atlantic.