bluuebunny/crossref_metadata_2025 huggingface dataset:
Complicating Voice in a Refusal to “Let Participants Speak for Themselves”
Authors: Mazzei Lisa A. , Jackson Alecia Y.
Published: October 2012

In this article, the authors respond to the editors’ call to challenge simplistic and mechanistic approaches to qualitative research that preclude dense and multilayered treatment of data. The editors assert that such practices can lead to (over)simplified knowledge claims, something especially risky when participant “voice” is presented as an expression of “experience” devoid of context. The authors approach the methodological project of a simplified voice in qualitative inquiry that attempts to offer an authentic essence or voice that is present, stable, and self-reflective. Aided by Deleuze to conceive a voice without an image, the authors specifically challenge simplistic treatments of voice that beckon voices to “speak for themselves” or that reduce complicated and conflicting voices to analytical “chunks” that can be interpreted free of context and circumstance. The authors conclude with illustrations from their research that demonstrate how they put such complicating practices to work and how they serve to open up previously unthought questions.
Exploring the dynamics of gender, feminism and entrepreneurship: advancing debate to escape a dead end?
Authors: Ahl Helene , Marlow Susan
Published: October 2012

Contrary to the neo-liberal thesis that entrepreneuring is an open and accessible endeavour where personal effort alone determines reward and status, it has been demonstrated that there is a persistent, but occluded, gender bias within the entrepreneurial discourse. Accordingly, women are positioned as lacking and incomplete men; however, despite calls to employ feminist theory as an analytical frame to demonstrate the reproduction of such subordination, there is scant evidence this has emerged. Within this article, we respond to this call by demonstrating how post structural feminist analysis reveals the gendered assumptions informing entrepreneurship theory that embed prevailing hetero-normative assumptions. These assumptions limit the epistemological scope of contemporary research which positions women as failed or reluctant entrepreneurial subjects; as such, in the absence of feminist theorizing these analyses remain descriptive rather than explanatory. Accordingly, the current entrepreneurial research agenda is in danger of reaching an epistemological dead end in the absence of a reflexive critical perspective to inform the idea of who can be and what might be an entrepreneur. Finally, we draw upon these arguments to reflect upon current approaches to theorizing within the broader field of entrepreneurial enquiry.
Pre-service teachers’ experiences implementing a hybrid curriculum
Authors: Stran Margaret , Sinelnikov Oleg , Woodruff Elizabeth
Published: October 2012

A hybrid Sport Education (SE) and Teaching Games for Understanding (TGfU) pedagogical model shifts responsibilities to students and enhances game play by focusing on tactical problems. The purpose of this study was to (1) examine pre-service teachers’ (PTs) perceptions teaching a SE-TGfU hybrid; and (2) identify facilitators and inhibitors that PTs experienced when implementing the model. Twenty-two PTs taught a hybrid SE-TGfU invasion games season to 162 students aged 10 to 11 years. Data included focus group interviews, critical incident reflections, daily lesson plans, and field notes. Data were analyzed using thematic analysis. Results indicate that PTs were attracted to the hybrid model due to its unique and complementary nature and perceived increased levels of student engagement in the class. However, most PTs had a surface understanding of the hybrid model and lacked the pedagogical content knowledge to make adjustments. The importance of early, field based exposure to new pedagogical models is highlighted.
Massive expansion of the calpain gene family in unicellular eukaryotes
Authors: Zhao Sen , Liang Zhe , Demko Viktor , Wilson Robert , Johansen Wenche , Olsen Odd-Arne , Shalchian-Tabrizi Kamran
Published: October 2012

Background

Calpains are Ca2+-dependent cysteine proteases that participate in a range of crucial cellular processes. Dysfunction of these enzymes may cause, for instance, life-threatening diseases in humans, the loss of sex determination in nematodes and embryo lethality in plants. Although the calpain family is well characterized in animal and plant model organisms, there is a great lack of knowledge about these genes in unicellular eukaryote species (i.e. protists). Here, we study the distribution and evolution of calpain genes in a wide range of eukaryote genomes from major branches in the tree of life.

Results

Our investigations reveal 24 types of protein domains that are combined with the calpain-specific catalytic domain CysPc. In total we identify 41 different calpain domain architectures, 28 of these domain combinations have not been previously described. Based on our phylogenetic inferences, we propose that at least four calpain variants were established in the early evolution of eukaryotes, most likely before the radiation of all the major supergroups of eukaryotes. Many domains associated with eukaryotic calpain genes can be found among eubacteria or archaebacteria but never in combination with the CysPc domain.

Conclusions

The analyses presented here show that ancient modules present in prokaryotes, and a few de novo eukaryote domains, have been assembled into many novel domain combinations along the evolutionary history of eukaryotes. Some of the new calpain genes show a narrow distribution in a few branches in the tree of life, likely representing lineage-specific innovations. Hence, the functionally important classical calpain genes found among humans and vertebrates make up only a tiny fraction of the calpain family. In fact, a massive expansion of the calpain family occurred by domain shuffling among unicellular eukaryotes and contributed to a wealth of functionally different genes.
Up-regulation of platelet-derived growth factor-A is responsible for the failure of re-initiated interferon alpha treatment in hepatocellular carcinoma
Authors: Zhang Ju-Bo , Sun Hui-Chuan , Jia Wei-Dong , Zhuang Peng-Yuan , Qian Yong-Bing , Zhu Xiao-Dong , Kong Ling-Qun , Wang Lu , Wu Wei-Zhong , Tang Zhao-You
Published: October 2012

Background

Postoperative interferon-α(IFN-α) treatment delays hepatocellular carcinoma(HCC) recurrence and prolongs patient survival, and may thus be an effective form of adjuvant therapy. However, clinical observations found that HCC recurs in some patients within 8 months of IFN-α treatment being discontinued. We investigated whether HCC regrowth appears after IFN-α is discontinued, whether re-initiated IFN-α is effective, and the underlying mechanisms of IFN-α treatment.

Methods

The human HCC nude mouse model LCI-D20 was used to study the effects of IFN-α treatment, discontinued IFN-α treatment, and re-initiated IFN-α treatment on tumor growth. Tumor weight, microvessel density(MVD), serum vascular endothelial growth factor (VEGF), and tumor cell apoptosis were analyzed. Angiogenesis-related factors were studied using cDNA microarray in different tumor samples and confirmed using reverse transcription–polymerase chain reaction(RT-PCR) and Western blotting assays. Finally, imatinib was added with re-initiated IFN-α treatment to improve efficacy.

Results

IFN-α (1.5×107 U/kg/day for 20 days) suppressed HCC growth by 60.3% and decreased MVD by 52.2% compared with the control. However, tumor regrowth occurred after IFN-α was discontinued, and re-initiated IFN-α treatment was not effective for inhibiting tumor growth or reducing MVD compared with a saline-treated group. cDNA microarray showed VEGF was down-regulated while platelet-derived growth factor-A (PDGF-A) was up-regulated when IFN-α treatment was re-initiated. These findings were further confirmed with RT-PCR and Western blotting assay. The combination of imatinib with re-initiated IFN-α reduced HCC weight by 30.7% and decreased MVD by 31.1% compared with IFN-α treatment only (P=0.003 and 0.015, respectively).

Conclusion

Tumor regrowth occurred after IFN-α treatment was discontinued. Re-initiated IFN-α treatment was not effective and was associated with up-regulation of PDGF-A, while the VEGF remained suppressed. The combination of a PDGF-receptor inhibitor with IFN-α improved the effect of the re-initiated treatment.
Analyses of body composition charts among younger and older Chinese children and adolescents aged 5 to 18 years
Authors: Xiong Kai-Yu , He Hui , Zhang Yi-Ming , Ni Guo-Xin
Published: October 2012

Background

Childhood obesity has become a major public health problem in China. The objective of this study was to examine the effect of age and sex on the relationship between fat-free mass (FFM) and fat mass (FM), fat-free mass index (FFMI) and fat mass index (FMI) in Chinese children using body composition chart analysis, and to compare the changing pattern with Caucasian and Japanese counterparts.

Methods

A total of 1458 children (790 boys and 668 girls) between 5 and 18 years of age were studied to determine a body composition by bioelectrical impedance analysis. The relationship of FFM and FM, FFMI and FMI were delineated by body composition charts.

Results

Different changing patterns in body composition were observed during 5-11y (younger age group), and 12-18y (older age group), with non-significant sex difference with FM and FMI for the younger age group and significant sex and age differences for the older age group. For the younger age group, simultaneous increase of FFM and FM was found in both genders. However, for the older age group, the increase in weight and BMI with age is largely due to the increment of FFM and FFMI in boys, and of FM and FMI in girls. In addition, different changing patterns in body composition exist between Chinese children and their Caucasian and Japanese counterparts, largely due to the higher fat mass component in Chinese subjects.

Conclusions

Our results indicate that age- and gender-related changing patterns of body composition in Chinese children may differ at different growth stage, and differ with those in Caucasian and Japanese children at the same age period. Such changing patterns should be considered when designing the intervention proposal for childhood obesity in China.
Changes in the expression of aromatase, estrogen receptor α and β in mandibular condylar cartilage of rats induced by disordered occlusion
Authors: Yu Shibin , Xing Xianghui , Jiao Kai , Sun Lei , Liu Lei , Wang Meiqing
Published: October 2012

Background

Estrogens play an important role in modulating the morphology and function of temporomandibular joints (TMJs), which is suggested to act via estrogen receptors (ERs). The present study was to investigate the expression of aggrecan, collagen type II (Col II), Col X, aromatase, ERα and ERβ in degenerative changes of mandibular condylar cartilage.

Methods

Forty male and 40 female 8-week-old rats were enrolled in this study. In experimental groups, the disordered occlusion was created by moving the first molars mesially and the third ones distally. Immunohistochemistry and real-time PCR were performed at the end of the second or fourth week.

Results

Degenerative changes, characterized by interrupted continuity of hypertrophic layer, pyknotic and eosinophilic lesion with few nuclei, areas filled with eosinophilic nuclei, were observed in more joints from female experimental groups than male ones. However, thickening changes in hypertrophic layer were only found in male experimental groups. The gene expression of Col II, Col X and aggrecan increased in 4-wk male experimental subgroup (both P < 0.01), but decreased in 2-wk and 4-wk female subgroups (P < 0.05). The gene expression of ERα decreased in 2-wk male and female experimental subgroups (both P < 0.01), however, that of ERβ increased except the 2-wk female experimental subgroup (all P < 0.01). The expression of aromatase decreased in both male and female experimental subgroups (all P<0.01).

Conclusions

Mandibular condylar cartilage responses differently to the disordered occlusion in male and female rats. The levels of locally synthesized estrogen, ERα and ERβ may have limited attribution, if any, to the sex-specific cartilage response.
Anti-cancer activity of novel dibenzo[b,f]azepine tethered isoxazoline derivatives
Authors: Sadashiva Maralinganadoddi Panchegowda , Basappa  , NanjundaSwamy Shivananju , Li Feng , Manu Kanjoormana Aryan , Sengottuvelan Murugan , Prasanna Doddakunche Shivaramu , Anilkumar Nirvanappa Chikkagundagal , Sethi Gautam , Sugahara Kazuyuki , Rangappa Kanchugarakoppal Subbegowda
Published: October 2012

Background

Dibenzoazepine (DB) derivatives are important and valuable compounds in medicinal chemistry. The synthesis and chemotherapeutic properties of naturally occurring DBs and different heterocyclic moiety tethered DBs are reported. Herein, we report the DB-fused hybrid structure that containing isoxazolines (DBIs) and their anti-cancer activity, which could throw light on the structural and functional features of new molecules.

Results and Conclusion

The synthesis and characterization of novel ring DB tethered isoxazoline derivatives (DBIs) were carried out. After the detailed structural characterization using 2D-NMR experiments, the compounds were identified as 5-substituted isoxazolines. The effect of newly synthesized DBIs against the invasion of murine osteosarcoma (LM8G7) cells was studied. Among the tested molecules, compound 4g (5-[−3-(4-chlorophenyl)-4,5-dihydroisoxazol-5-yl-methyl]-5 H- dibenzo[b,f]azepine), was found to inhibit the invasion of LM8G7 cells strongly, when compared to other structurally related compounds. Cumulatively, the compound 4g inhibited the invasion MDA-MB-231 cells completely at 10 μM. In addition to anti-invasion property the compound 4g also inhibited the migration of LM8G7 and human ovarian cancer cells (OVSAHO) dose-dependently. Compound 4g inhibited the proliferation of LM8G7, OVSAHO, human breast cancer cells (MCF-7) and human melphalan-resistant multiple myeloma (RPMI8226-LR5) cells that are comparable to cisplatin and suramin.
Evaluation of gut modulatory and bronchodilator activities of Amaranthus spinosus Linn.
Authors: Chaudhary Mueen Ahmad , Imran Imran , Bashir Samra , Mehmood Malik Hassan , Rehman Najeeb-ur , Gilani Anwarul-Hassan
Published: October 2012

Background

The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses.

Methods

The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms.

Results

In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 and 300 mg/kg showing laxative activity. It also inhibited carbachol-induced bronchospasm in anesthetized rats at 1, 3, 10 and 30 mg/kg indicative of bronchodilator activity. When tested on isolated gut preparations, the plant extract showed a concentration-dependent (0.01-10.0 mg/ml) spasmogenic effect in spontaneously contracting rabbit jejunum and guinea-pig ileum. The spasmogenic effect was partially blocked in tissues pretreated with atropine (0.1 μM). When tested on K+ (80 mM)-induced sustained contractions in isolated rabbit jejunum, the plant extract caused complete relaxation and also produced a shift in the Ca++ concentration-response curves (CRCs) towards right, similar to diltiazem. In rabbit trachea, the plant extract completely inhibited K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions at 1 mg/ml but pretreatment of tissue with propranolol (1 μM), caused around 10 fold shift in the inhibitory CRCs of the plant extract constructed against CCh-induced contraction. The plant extract (up to 0.3 mg/ml) also increased both force and rate of spontaneous contractions of isolated guinea-pig atria, followed by relaxation at higher concentration (1.0-5.0 mg/ml). The cardio-stimulant effect was abolished in the presence of propranolol, similar to that of isoprenaline. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the organic fraction, whereas the spasmogenic component was concentrated in the aqueous fraction.

Conclusion

These results indicate that A. spinosus possesses laxative activity partially mediated through cholinergic action. The spasmolytic effect was mediated through calcium channel blocking (CCB), while bronchodilator activity through a combination of β-adrenergic and CCB pathways, which may explain the traditional uses of A. spinosus in gut and airways disorders.
Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study
Authors: Kim Kab-Choong , Yook Jeong-Hwan , Eisenbraun Jürgen , Kim Byung-Sik , Huber Roman
Published: October 2012

Background

Mistletoe (Viscum album L.) extracts are widely used in complementary cancer therapy. Aim of this study was to evaluate safety and efficacy of a standardized mistletoe extract (abnobaVISCUM® Quercus, aVQ) in patients with gastric cancer.

Patients and Methods

32 operated gastric cancer patients (stage Ib or II) who were waiting for oral chemotherapy with the 5-FU prodrug doxifluridine were randomized 1:1 to receive additional therapy with aVQ or no additional therapy. aVQ was injected subcutaneously three times per week from postoperative day 7 to week 24 in increasing doses. EORTC QLQ-C30 and -STO22 Quality of Life questionnaire, differential blood count, liver function tests, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-2), CD 16+/CD56+ and CD 19+ lymphocytes were analyzed at baseline and 8, 16 and 24 weeks later.

Results

Global health status (p <0.01), leukocyte- and eosinophil counts (p ≤0.01) increased significantly in the treatment group compared to the control group. Diarrhea was less frequently reported (7% vs. 50%, p=0.014) in the intervention group. There was no significant treatment effect on levels of TNF-alpha, IL-2, CD16+/CD56+ and CD 19+ lymphocytes and liver function tests measured by ANOVA.

Conclusion

Additional treatment with aVQ is safe and was associated with improved QoL of gastric cancer patients. ClinicalTrials.Gov Registration number NCT01401075.
Common fixed-point results in uniformly convex Banach spaces
Authors: Akkasriworn Naknimit , Kaewkhao Annop , Keawkhao Attapol , Sokhuma Kritsana
Published: October 2012

We introduce a condition on mappings, namely condition

(
K
)

. In a uniformly convex Banach space, the condition is weaker than quasi-nonexpansiveness and weaker than asymptotic nonexpansiveness. We also present the existence theorem of common fixed points for a commuting pair consisting of a mapping satisfying condition

(
K
)

and a multivalued mapping satisfying conditions

(
E
)

and

(

C
λ

)

for some

λ
∈
(
0
,
1
)

.
Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer’s disease
Authors: Saito Yuhki , Inoue Tsuyoshi , Zhu Gang , Kimura Naoki , Okada Motohiro , Nishimura Masaki , Kimura Nobuyuki , Murayama Shigeo , Kaneko Sunao , Shigemoto Ryuichi , Imoto Keiji , Suzuki Toshiharu
Published: October 2012

Background

One of the best-characterized causative factors of Alzheimer’s disease (AD) is the generation of amyloid-β peptide (Aβ). AD subjects are at high risk of epileptic seizures accompanied by aberrant neuronal excitability, which in itself enhances Aβ generation. However, the molecular linkage between epileptic seizures and Aβ generation in AD remains unclear.

Results

X11 and X11-like (X11L) gene knockout mice suffered from epileptic seizures, along with a malfunction of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Genetic ablation of HCN1 in mice and HCN1 channel blockage in cultured Neuro2a (N2a) cells enhanced Aβ generation. Interestingly, HCN1 levels dramatically decreased in the temporal lobe of cynomolgus monkeys (Macaca fascicularis) during aging and were significantly diminished in the temporal lobe of sporadic AD patients.

Conclusion

Because HCN1 associates with amyloid-β precursor protein (APP) and X11/X11L in the brain, genetic deficiency of X11/X11L may induce aberrant HCN1 distribution along with epilepsy. Moreover, the reduction in HCN1 levels in aged primates may contribute to augmented Aβ generation. Taken together, HCN1 is proposed to play an important role in the molecular linkage between epileptic seizures and Aβ generation, and in the aggravation of sporadic AD.
Inactivation of Bacillus cereus vegetative cells by gastric acid and bile during in vitro gastrointestinal transit
Authors: Ceuppens Siele , Uyttendaele Mieke , Hamelink Stefanie , Boon Nico , Van de Wiele Tom
Published: October 2012

Background

The foodborne pathogen Bacillus cereus can cause diarrhoeal food poisoning by production of enterotoxins in the small intestine. The prerequisite for diarrhoeal disease is thus survival during gastrointestinal passage.

Methods

Vegetative cells of 3 different B. cereus strains were cultivated in a real composite food matrix, lasagne verde, and their survival during subsequent simulation of gastrointestinal passage was assessed using in vitro experiments simulating transit through the human upper gastrointestinal tract (from mouth to small intestine).

Results

No survival of vegetative cells was observed, despite the high inoculum levels of 7.0 to 8.0 log CFU/g and the presence of various potentially protective food components. Significant fractions (approx. 10% of the consumed inoculum) of B. cereus vegetative cells survived gastric passage, but they were subsequently inactivated by bile exposure in weakly acidic intestinal medium (pH 5.0). In contrast, the low numbers of spores present (up to 4.0 log spores/g) showed excellent survival and remained viable spores throughout the gastrointestinal passage simulation.

Conclusion

Vegetative cells are inactivated by gastric acid and bile during gastrointestinal passage, while spores are resistant and survive. Therefore, the physiological form (vegetative cells or spores) of the B. cereus consumed determines the subsequent gastrointestinal survival and thus the infective dose, which is expected to be much lower for spores than vegetative cells. No significant differences in gastrointestinal survival ability was found among the different strains. However, considerable strain variability was observed in sporulation tendency during growth in laboratory medium and food, which has important implications for the gastrointestinal survival potential of the different B. cereus strains.
Workshop report: Can an understanding of the mechanisms underlying age-related loss of muscle mass and function guide exercise and other intervention strategies?
Authors: Jackson Malcolm J , McArdle Anne , Vasilaki Aphrodite , Kayani Anna
Published: October 2012

An international workshop was hosted by the University of Liverpool on 15–16 July 2011 to address at a basic level what is known about the fundamental mechanisms by which skeletal muscle mass and function are lost during aging and to examine the nature of interventions that might prevent these mechanistic changes. Of particular importance was to attempt to evaluate how different forms of exercise (or muscle contractile activity) influence these processes and how these effects can be best optimized to prevent or delay age-related loss of muscle function. The program took the form of a two-day meeting, comprising a series of invited talks and breakout sessions designed to identify key gaps in current knowledge and potential future research questions. The aims of this Workshop were two-fold: 1. To identify the current state-of-the-art in the understanding of the mechanisms that contribute to loss of skeletal muscle mass and function that occurs with aging and to address at a mechanistic level how, and to what extent, exercise and/or other interventions might prevent these changes. 2. To identify specific areas of research where information is sparse but which are likely to yield data that will impact on future strategies to manipulate age-related loss of muscle mass and function in older people. The areas discussed in detail were loss of functional motor units, reduced muscle stem cell activity, age-related changes in transcriptional responses of muscle to exercise and nutrition, age-related changes in protein homeostasis, mitochondrial function, altered cross-talk between muscle with immune cells and how the developments in basic science to understand mechanisms underlying age-related loss of muscle mass and function can be translated. Following each session three key areas where further studies are needed were identified.
Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study
Authors: Vaz-Luis Ines , Ottesen Rebecca A , Hughes Melissa E , Marcom P Kelly , Moy Beverly , Rugo Hope S , Theriault Richard L , Wilson John , Niland Joyce C , Weeks Jane C , Lin Nancy U
Published: October 2012

Introduction

In gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status.

Methods

We evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups.

Results

Median follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002).

As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had significantly increased hazard of early, but not late, death (hazard ratio of death zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19 to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI: 0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of diagnosis).

Conclusions

Presenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials.
Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome
Authors: Wada Takeshi , Jesmin Subrina , Gando Satoshi , Yanagida Yuichiro , Mizugaki Asumi , Sultana Sayeeda N , Zaedi Sohel , Yokota Hiroyuki
Published: October 2012

Introduction

Post-cardiac arrest syndrome (PCAS) often leads to multiple organ dysfunction syndrome (MODS) with a poor prognosis. Endothelial and leukocyte activation after whole-body ischemia/reperfusion following resuscitation from cardiac arrest is a critical step in endothelial injury and related organ damage. Angiogenic factors, including vascular endothelial growth factor (VEGF) and angiopoietin (Ang), and their receptors play crucial roles in endothelial growth, survival signals, pathological angiogenesis and microvascular permeability. The aim of this study was to confirm the efficacy of angiogenic factors and their soluble receptors in predicting organ dysfunction and mortality in patients with PCAS.

Methods

A total of 52 resuscitated patients were divided into two subgroups: 23 survivors and 29 non-survivors. The serum levels of VEGF, soluble VEGF receptor (sVEGFR)1, sVEGFR2, Ang1, Ang2 and soluble Tie2 (sTie2) were measured at the time of admission (Day 1) and on Day 3 and Day 5. The ratio of Ang2 to Ang1 (Ang2/Ang1) was also calculated. This study compared the levels of angiogenic factors and their soluble receptors between survivors and non-survivors, and evaluated the predictive value of these factors for organ dysfunction and 28-day mortality.

Results

The non-survivors demonstrated more severe degrees of organ dysfunction and a higher prevalence of MODS. Non-survivors showed significant increases in the Ang2 levels and the Ang2/Ang1 ratios compared to survivors. A stepwise logistic regression analysis demonstrated that the Ang2 levels or the Ang2/Ang1 ratios on Day 1 independently predicted the 28-day mortality. The receiver operating characteristic curves of the Ang2 levels, and the Ang2/Ang1 ratios on Day 1 were good predictors of 28-day mortality. The Ang2 levels also independently predicted increases in the Sequential Organ Failure Assessment (SOFA) scores.

Conclusions

We observed a marked imbalance between Ang1 and Ang2 in favor of Ang2 in PCAS patients, and the effect was more prominent in non-survivors. Angiogenic factors and their soluble receptors, particularly Ang2 and Ang2/Ang1, are considered to be valuable predictive biomarkers in the development of organ dysfunction and poor outcomes in PCAS patients.
Relation between proteinuria and acute kidney injury in patients with severe burns
Authors: Hu Jiong Yu , Meng Xin Chun , Han Jian , Xiang Fei , Fang Ya Dong , Wu Jun , Peng Yi Zhi , Wu Ya Zhou , Huang Yue Sheng , Luo Qi Zhi
Published: October 2012

Introduction

Proteinuria in burn patients is common, and may be associated with acute kidney injury (AKI) and adverse outcomes. We evaluated the incidences, outcomes, characteristics and determinants of proteinuria and its influence on AKI and outcomes in burn patients.

Methods

This retrospective study was carried out in a hospital's burn department. The study population consisted of patients with burn injuries admitted during a five-year period. Positive urine dipstick readings were defined as mild (± or 1+) or heavy (≥ 2+) proteinuria, and AKI was diagnosed and staged according to the Risk, Injury, Failure, Loss, End Stage (RIFLE) classification system. Patient characteristics, management and outcomes were evaluated for associations with proteinuria using nonparametric tests, chi-square (χ2) tests and binary logistic regression.

Results

Of the patients admitted to the burn unit during the study period (n = 2,497), 865 (34.64%) were classified as having proteinuria. In the patients whose total burn surface areas (TBSA) were > 30% (n = 396), 271 patients (68.43%) had proteinuria and 152 of these patients (56.09%) met AKI criteria. No patients without proteinuria developed AKI. Intensive care unit (ICU) mortality rates were 0.8%, 16.67% and 30.77% (P < 0.001) in the groups with no, mild and heavy proteinuria, respectively. Logistic regression analysis identified proteinuria (OR 4.48; 95% CI, 2.824 to 7.108; P < 0.001) and sequential organ failure assessment (OR 1.383; 95% CI, 1.267 to 1.509; P < 0.001) as risk factors for AKI.

Conclusions

We observed a high prevalence of proteinuria in patients with severe burns (> 30% TBSA). Severely burned patients with proteinuria had a high risk of developing AKI and a poor prognosis for survival. This suggests that proteinuria should be used for identifying burn patients at risk of developing AKI.
An observational study to determine the effect of delayed admission to the intensive care unit on patient outcome
Authors: O'Callaghan David JP , Jayia Parveen , Vaughan-Huxley Eyston , Gribbon Michael , Templeton Maie , Skipworth James RA , Gordon Anthony C
Published: October 2012

Introduction

Delayed patient admission to the intensive care unit (ICU) due to lack of bed availability is a common problem, but the effect on patient outcome is not fully known.

Methods

A retrospective study was performed using departmental computerised records to determine the effect of delayed ICU admission and temporary management within the operating theatre suite on patient outcome. Emergency surgical and medical patients admitted to the ICU (2003 to 2007) were divided into delay (more than three hours from referral to admission) and no-delay (three or fewer hours from referral to admission) groups. Our primary outcome measure was length of ICU stay. Secondary outcome measures were mortality rates and duration of organ support.

Results

A total of 1,609 eligible patients were included and 149 (9.3%) had a delayed admission. The delay and no-delay groups had similar baseline characteristics. Median ICU stay was 5.1 days (delay) and 4.5 days (no-delay) (P = 0.55) and ICU mortality was 26.8% (delay) and 24.2% (no-delay) (P = 0.47). Following adjustment for demographic and baseline characteristics there was no difference in either length of ICU stay or mortality rates between groups. ICU admission delay was associated with both an increased requirement for advanced respiratory support (92.3% delay vs. 76.4% no-delay, P <0.01) and a longer time spent ventilated (median four days delay vs. three days no-delay, P = 0.04).

Conclusions

No significant difference in length of ICU stay or mortality rate was demonstrated between the delay and no-delay cohorts. Patients within the delay group had a significantly greater requirement for advanced respiratory support and spent a longer time ventilated.
Aging effects on DNA methylation modules in human brain and blood tissue
Authors: Horvath Steve , Zhang Yafeng , Langfelder Peter , Kahn René S , Boks Marco PM , van Eijk Kristel , van den Berg Leonard H , Ophoff Roel A
Published: October 2012

Background

Several recent studies reported aging effects on DNA methylation levels of individual CpG dinucleotides. But it is not yet known whether aging-related consensus modules, in the form of clusters of correlated CpG markers, can be found that are present in multiple human tissues. Such a module could facilitate the understanding of aging effects on multiple tissues.

Results

We therefore employed weighted correlation network analysis of 2,442 Illumina DNA methylation arrays from brain and blood tissues, which enabled the identification of an age-related co-methylation module. Module preservation analysis confirmed that this module can also be found in diverse independent data sets. Biological evaluation showed that module membership is associated with Polycomb group target occupancy counts, CpG island status and autosomal chromosome location. Functional enrichment analysis revealed that the aging-related consensus module comprises genes that are involved in nervous system development, neuron differentiation and neurogenesis, and that it contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease. A comparison with a standard, non-module based meta-analysis revealed that selecting CpGs based on module membership leads to significantly increased gene ontology enrichment, thus demonstrating that studying aging effects via consensus network analysis enhances the biological insights gained.

Conclusions

Overall, our analysis revealed a robustly defined age-related co-methylation module that is present in multiple human tissues, including blood and brain. We conclude that blood is a promising surrogate for brain tissue when studying the effects of age on DNA methylation profiles.
Dendritic cell science: more than 40 years of history
Authors: van Spriel Annemiek B , de Jong Esther C
Published: October 2012

Historical overview of the major milestones and discoveries in dendritic cell science.

Over 40 years of research into the field of DCs has revolutionized our understanding into the activation and regulation of the immune system. This minireview discusses the major breakthroughs in DC science that have paved the way to the 2011 Nobel Prize in Physiology-Medicine awarded to Bruce A. Beutler and Jules A. Hoffmann (for their discoveries in innate immune recognition) and Ralph M. Steinman (for his discovery of the DC).
Penetration of Time to Change leaflets on stigmatised attitudes to people with mental illness
Authors: Mendes Vania , Easow Joby Maducolil , Luty Jason
Published: October 2012

Aims and method

To determine whether members of the general public read a leaflet from the Time to Change anti-stigma campaign. The leaflets were sent to 1000 members of the public at random. Those who read the leaflet were asked, in a statement concealed within the text, to return it. A second study involved modified leaflets being posted to 400 members of a representative panel of the UK general public.

Results

Only 20 of the 1000 (2%) people who received the unsolicited leaflet returned them, which suggests that the vast majority were unread. However, the leaflet achieved a good response in the sample from the research panel with at least 29% of participants (115 of 400) reading the leaflet.

Clinical implications

A very small proportion of people acknowledge unsolicited leaflets. However, the leaflet was read by almost a third of a research panel. Hence, few people are likely to read unsolicited leaflets, including those containing a public health message.
Mixed-methods evaluation of a leadership development programme for higher specialist trainees
Authors: Healey Christine , Fearnley David , Chivers Mandy , Wadoo Ovais , Kinderman Peter
Published: October 2012

Aims and method

Newly appointed consultant psychiatrists have reported that management and leadership is an area for which they are unprepared. Our aim was to evaluate the impact of a leadership development programme based on the principles of ‘action learning’ for higher trainees. A questionnaire survey was sent to 54 trainees and consultants who had attended the programme. Qualitative interviews were conducted with 15 participants using the concept of maximum variance sampling.

Results

The relevance of the topics covered, the opportunity for free discussion and increased understanding of National Health Service policy were rated highest. At the end of a thematic analysis, themes were organised into four major categories: (a) lack of engagement with management during training; (b) the lasting impact of the leadership development programme; (c) understanding the larger organisational context; and (d) transition to consultant psychiatrist.

Clinical implications

The findings suggest that programmes such as this can be successful in raising awareness and increasing engagement in medical leadership and management.
The Oxide–Water Interface: How Valid Is the Site Dissociation–Surface Equilibria Model?
Authors: Healy Thomas W , Scales Peter J
Published: October 2012

The great Dutch school of colloid science of Kruyt, Overbeek, and others developed theoretical and experimental models of the silver halide–water interface. Potentiometric titrations, electrokinetic measurements, and coagulation kinetics set high standards of experimentation. They, further, led to the development of theoretical models, mostly thermodynamic, of the silver halide–aqueous electrolyte interface, which allowed quantitative understanding of experimental results. The fundamental step was to recognize that silver and halide ions, as potential-determining ions, controlled the Nernst potential of the interface. At ca. 25 °C, as the concentration of silver ions in the bulk solution changed by a factor of 10, the potential of the silver halide–water interface changed by 59 mV. Colloid scientists across the globe in the post-1948 era, additionally wished to understand the properties of colloidal dispersions of simple inorganic oxides such as silica, hematite, and alumina, and more recently, the properties of “latex” particles. In short, it became difficult to apply the theories that allowed understanding of the silver halide–water interface to the understanding of the properties of latex, oxides, and similar colloidal dispersions. Finally, a very recent resurgence in the interest in the electrical double layer (e.d.l.) at the air–water and oil–water interface has fuelled the discussion on the ubiquitous role of protons as potential-determining ions (p.d.i.’s) on interfaces ranging from oxides, to lattices, close packed monolayers, and oil–water and air–water interfaces. We explore the new thinking on all of these aqueous interfaces.
Ionic Self-assembled Fluorescent Organic Nanosticks
Authors: Lv Chao , Xu Guanchen , Chen Xiao
Published: October 2012

Stable fluorescent organic nanosticks were fabricated via a facile ionic self-assembly (ISA) route through complexation between p-aminoazobenzene hydrochloride (AzoHCl) and sodium deoxycholate (NaDC) molecules in solution. Transmission and scanning electron microscopic (TEM and SEM) observations and fluorescence spectroscopy techniques were used to characterize the nanostick structure and the self-assembling mechanism.
Dyslipidemia: Management Using Optimal Lipid-Lowering Therapy
Authors: Ito Matthew K
Published: October 2012

Objective:

To evaluate current approaches and explore emerging research related to dyslipidemia management.

Data Sources:

MEDLINE (2004-April 2012) was searched for randomized controlled trials using the terms dyslipidemia and lipid-lowering therapy or statin (>1000 hits). Separate searches (MEDLINE, Google) identified meta-analyses (2010–2011), disease prevalence statistics, and current consensus guidelines (2004–July 2011). Additional references were identified from the publications reviewed.

Study Selection and Data Extraction:

English-language articles on large multi-center trials were evaluated.

Data Synthesis:

National Cholesterol Education Program Adult Treatment Panel III guidelines for the reduction of cardiovascular risk recommend the attainment of specific low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol (non–HDL-C) target values, based on an individual's 10-year risk of coronary heart disease or global risk. For most patients unable to achieve recommended lipid level goals with therapeutic lifestyle changes, statins are the first option for treatment. Results of large, well-controlled clinical trials have demonstrated that statins are effective in primary and secondary prevention of cardiovascular disease in diverse populations, including patients with diabetes and the elderly, and that intensive statin therapy provides more effective lipid goal attainment and significantly greater risk reduction in patients with coronary artery disease. Stalin therapy is generally well tolerated but may increase the risk of myopathy. Statin use has been associated with increases in hepatic transaminases and an increased risk of diabetes, although the absolute risk of diabetes is low compared with the risk reduction benefit. Combination therapy including a statin may be appropriate for certain populations, but the risk reduction benefits of combination therapy remain unclear. Ezetimibe is an important treatment option for patients with hypercholesterolemia who do not tolerate intensive statin therapy. Although fibrates or niacin improves overall lipid profiles in patients with hypertriglyceridemia or dyslipidemia who are receiving statin therapy, their efficacy in reducing cardiovascular risk remains questionable and their use raises safety and tolerability concerns.

Conclusions:

Intensifying lifestyle changes and statin dose should be utilized first in patients not achieving their LDL-C and non-HDL-C goals.
Inhibitory Metabolic Drug Interactions with Newer Psychotropic Drugs: Inclusion in Package Inserts and Influences of Concurrence in Drug Interaction Screening Software
Authors: Boyce Richard D , Collins Carol , Clayton Marc , Kloke John , Horn John R
Published: October 2012

Background:

Food and Drug Administration (FDA) regulations mandate that package inserts (Pls) include observed or predicted clinically significant drug-drug interactions (DDIs), as well as the results of pharmacokinetic studies that establish the absence of effect.

Objective:

To quantify how frequently observed metabolic inhibition DDIs affecting US-marketed psychotropics are present in FDA-approved Pls and what influence the source of DDI information has on agreement between 3 DDI screening programs.

Methods:

The scientific literature and Pls were reviewed to determine all drug pairs for which there was rigorous evidence of a metabolic inhibition interaction or noninteraction. The DDIs were tabulated noting the source of evidence and the strength of agreement over chance. Descriptive statistics were used to examine the influence of source of DDI information on agreement among 3 DDI screening tools. Logistic regression was used to assess the influence of drug class, indication, generic status, regulatory approval date, and magnitude of effect on agreement between the literature and PI as well as agreement among the DDI screening tools.

Results:

Thirty percent (13/44) of the metabolic inhibition DDIs affecting newer psychotropics were not mentioned in Pls. Drug class, indication, regulatory approval date, generic status, or magnitude of effect did not appear to be associated with more complete DDI information in Pls. DDIs found exclusively in Pls were 3.25 times more likely to be agreed upon by all 3 DDI screening tools than were those found exclusively in the literature. Generic status was inversely associated with agreement among the DDI screening tools (odds ratio 0.11; 95% CI 0.01 to 0.89).

Conclusions:

The presence in Pls of DDI information for newer psychotropics appears to have a strong influence on agreement among DDI screening tools. Users of DDI screening software should consult more than 1 source when considering interactions involving generic psychotropics.
Support Needs of Siblings of People with Developmental Disabilities
Authors: Arnold Catherine K. , Heller Tamar , Kramer John
Published: October 2012

This qualitative study examines the support needs of adult siblings of people with developmental disabilities. A survey completed by 139 siblings of people with developmental disabilities captured the needs of adult siblings through 2 open-ended questions. A grounded theory approach was used, and the sibling responses anchored the analysis, interpretation of findings, and discussion using the constant comparison method. Eleven core variables and 3 overarching themes emerged. Three overarching themes for sibling support needs include: (a) getting disability-related information, (b) getting support for their caregiving role, and (c) enhancing the formal support system to address sibling needs.