bluuebunny/crossref_metadata_2025 huggingface dataset:
A structured framework for assessing sensitivity to missing data assumptions in longitudinal clinical trials
Authors: Mallinckrodt C.H. , Lin Q. , Molenberghs M.
Published: November 2012

The objective of this research was to demonstrate a framework for drawing inference from sensitivity analyses of incomplete longitudinal clinical trial data via a re‐analysis of data from a confirmatory clinical trial in depression. A likelihood‐based approach that assumed missing at random (MAR) was the primary analysis. Robustness to departure from MAR was assessed by comparing the primary result to those from a series of analyses that employed varying missing not at random (MNAR) assumptions (selection models, pattern mixture models and shared parameter models) and to MAR methods that used inclusive models. The key sensitivity analysis used multiple imputation assuming that after dropout the trajectory of drug‐treated patients was that of placebo treated patients with a similar outcome history (placebo multiple imputation). This result was used as the worst reasonable case to define the lower limit of plausible values for the treatment contrast. The endpoint contrast from the primary analysis was − 2.79 (p  =  .013). In placebo multiple imputation, the result was − 2.17. Results from the other sensitivity analyses ranged from − 2.21 to − 3.87 and were symmetrically distributed around the primary result. Hence, no clear evidence of bias from missing not at random data was found. In the worst reasonable case scenario, the treatment effect was 80% of the magnitude of the primary result. Therefore, it was concluded that a treatment effect existed. The structured sensitivity framework of using a worst reasonable case result based on a controlled imputation approach with transparent and debatable assumptions supplemented a series of plausible alternative models under varying assumptions was useful in this specific situation and holds promise as a generally useful framework. Copyright © 2012 John Wiley & Sons, Ltd.
Pimarane‐type Diterpenes Obtained by Biotransformation: Antimicrobial Properties Against Clinically Isolated Gram‐positive Multidrug‐resistant Bacteria
Authors: Porto Thiago S. , Simão Marília R. , Carlos Lucas Z. , Martins Carlos H. G. , Furtado Niege A. J. C. , Said Suraia , Arakawa Nilton S. , dos Santos Raquel A. , Veneziani Rodrigo C. S. , Ambrósio Sérgio R.
Published: November 2012

The present study describes the antimicrobial activity of five pimarane‐type diterpenes obtained by fungal biotransformation against several nosocomial multidrug‐resistant bacteria. Among the investigated metabolites, ent‐8(14),15‐pimaradien‐3β‐ol was the most active compound, with very promising minimal inhibitory concentration values (between 8.0 and 25.0 µg mL−1). Time‐kill assays using this metabolite against Staphylococcus aureus (HCRP180) revealed that this compound exerted its bactericidal effect within 24 h at all the evaluated concentrations (8.0, 16.0, and 24.0 µg mL−1). When this metabolite was associated with vancomycin at their minimal bactericidal concentration values, the resulting combination was able to drastically reduce the number of viable strains of S. aureus within the first 6 h, compared with these chemicals alone. The checkerboard assays conducted against this microorganism did not evidence any synergistic effects when this same combination was employed. In conclusion, our results point out that ent‐8(14),15‐pimaradien‐3β‐ol is an important metabolite in the search for new effective antimicrobial agents. Copyright © 2012 John Wiley & Sons, Ltd.
Apoptosis‐inducing and Antitumor Activity of Neolignans Isolated from Magnolia officinalis in HeLa Cancer Cells
Authors: Youn Ui Joung , Fatima Nighat , Chen Quan Cheng , Chae Sungwook , Hung Tran Manh , Min Byung‐Sun
Published: November 2012

Two neolignans, 4′‐methoxymagndialdehyde (1) and magnaldehyde B (2), were isolated from the stem bark of Magnolia officinalis (Magnoliaceae), evaluated for apoptosis‐inducing effects in human cervical epitheloid carcinoma HeLa cells. The apoptosis‐inducing activity of compounds 1 and 2 were assessed by DNA content using flow cytometric analysis. In the immunoblotting analysis, the treatment with 1 and 2 resulted in the cleavage of procaspase‐8 and ‐3 and poly(ADP‐ribose)polymerase into active forms. In addition, in vivo, the administration of 2 to Lewis lung carcinoma‐inoculated mice evidenced a significant inhibition of tumor growth (volume) with reduction of 28.7% at concentration of 20 mg/kg, as compared with the control mice. These findings suggest that 2 can inhibit the proliferation of tumor cells, and might be an anti‐tumoric agent. Copyright © 2012 John Wiley & Sons, Ltd.
Cardiovascular Protection and Antioxidant Activity of the Extracts from the Mycelia of Cordyceps Sinensis Act Partially Via Adenosine Receptors
Authors: Yan Xiao‐Feng , Zhang Zhong‐Miao , Yao Hong‐Yi , Guan Yan , Zhu Jian‐Ping , Zhang Lin‐Hui , Jia Yong‐Liang , Wang Ru‐Wei
Published: November 2012

Mycelia of cultured Cordyceps sinensis (CS) is one of the most common substitutes for natural CS and was approved for arrhythmia in China. However, the role of CS in ameliorating injury during ischemia‐reperfusion (I/R) is still unclear. We examined effects of extracts from CS on I/R and investigated the possible mechanisms. Post‐ischemic coronary perfusion pressure, ventricular function, and coronary flow were measured using the Langendorff mouse heart model. Oxidative stress of cardiac homogenates was performed using an ELISA. Our results indicate that CS affords cardioprotection possibly through enhanced adenosine receptor activation. Cardioprotection was demonstrated by reduced post‐ischemic diastolic dysfunction and improved recovery of pressure development and coronary flow. Treatment with CS largely abrogates oxidative stress and damage in glucose‐ or pyruvate‐perfused hearts. Importantly, observed reductions in oxidative stress [glutathione disulfide (GSSG)]/[GSSG + glutathione] and [malondialdehyde (MDA)]/[superoxide dismutase + MDA] ratios as well as the resultant damage upon CS treatment correlate with functional markers of post‐ischemic myocardial outcome. These effects of CS were partially blocked by 8‐ρ‐sulfophenyltheophylline, an adenosine receptor antagonist. Our results demonstrate a suppressive role of CS in ischemic contracture. Meanwhile, the results also suggest pre‐ischemic adenosine receptor activation may be involved in reducing contracture in hearts pretreated with CS. Copyright © 2012 John Wiley & Sons, Ltd.
Technical skills measurement based on a cyber‐physical system for endovascular surgery simulation
Authors: Tercero Carlos , Kodama Hirokatsu , Shi Chaoyang , Ooe Katsutoshi , Ikeda Seiichi , Fukuda Toshio , Arai Fumihito , Negoro Makoto , Kwon Guiryong , Najdovski Zoran
Published: November 2012

Background

Quantification of medical skills is a challenge, particularly simulator‐based training. In the case of endovascular intervention, it is desirable that a simulator accurately recreates the morphology and mechanical characteristics of the vasculature while enabling scoring.

Methods

For this purpose, we propose a cyber‐physical system composed of optical sensors for a catheter's body motion encoding, a magnetic tracker for motion capture of an operator's hands, and opto‐mechatronic sensors for measuring the interaction of the catheter tip with the vasculature model wall. Two pilot studies were conducted for measuring technical skills, one for distinguishing novices from experts and the other for measuring unnecessary motion.

Results

The proficiency levels were measurable between expert and novice and also between individual novice users. The results enabled scoring of the user's proficiency level, using sensitivity, reaction time, time to complete a task and respect for tissue integrity as evaluation criteria. Additionally, unnecessary motion was also measurable.

Conclusion

The development of cyber‐physical simulators for other domains of medicine depend on the study of photoelastic materials for human tissue modelling, and enables quantitative evaluation of skills using surgical instruments and a realistic representation of human tissue. Copyright © 2012 John Wiley & Sons, Ltd.
Proteins in the gas phase
Authors: Meyer Tim , Gabelica Valérie , Grubmüller Helmut , Orozco Modesto
Published: November 2012

Proteins are complex macromolecules that evolved over billions of years to be active in aqueous solution. Water is a key element that stabilizes their structure, and most structural studies on proteins have thus been carried out in aqueous environment. However, recent experimental approaches have opened the possibility to gain structural information on proteins from gas‐phase measurements. The obtained results revealed significant structural memory in proteins when transferred from water to the gas phase. However, after several years of experimental and theoretical research, the nature of the structural changes induced by vaporization, the exact characteristics of proteins in the gas phase, and the physicochemical forces stabilizing dehydrated proteins are still unclear. We will review here these issues using both experimental and theoretical sources of information. © 2012 John Wiley & Sons, Ltd.

This article is categorized under:

Molecular and Statistical Mechanics > Molecular Interactions
Synthesis, Structure, and Characterization of Two Zn/Cd Coordination Polymers with Flexible Disulfide Carboxylate Derivatives
Authors: Chen Xiao‐Li , Qiao Ya‐Li , Gao Lou‐Jun , Cui Hua‐Li , Zhang Mei‐Li , Lv Jun‐Fang , Hou Xiang‐Yang
Published: November 2012

Two novel d10 metal coordination polymers [Cd2(Hmna)4]n (1), [Zn2(ddca)2 (dpe)]n·nH2O (2) (H2mna = 6‐mercaptonicotinic acid, H2ddca = 6, 6'‐dithiodinicotinic acid, dpe = 1, 2‐bis(4‐pyridyl)ethylene), were hydrothermally synthesized and characterized by single‐crystal X‐ray diffraction. Compound 1 is a cyclic double chain structure containing 16‐number and 32‐number circles with (Hmna)– ligands as bridges, in which the starting H2ddca reagent was unprecedentedly converted into H2mna ligands via in situ cleavage of S–S bonds during the course of hydrothermal treatment. In compound 2, two five‐coordinate zinc centers are connected with carboxylate groups of H2ddca ligands to give a binuclear [Zn2(CO2)4] unit, which are linked by dpe ligands to form a 2D network structure. It is worth noting that compound 2 displays a twofold 2D+2D parallel interpenetration framework containing a polyrotaxane‐like motif. In addition, the thermal stablities and photoluminescence properties of compounds 1 and 2 were also studied.
Laparoscopic Versus Open Surgery for Stage I Rectal Cancer: Long‐term Oncologic Outcomes
Authors: Lee Seung Duk , Park Sung Chan , Park Ji Won , Kim Dae Yong , Choi Hyo Seong , Oh Jae Hwan
Published: November 2012

Background

Laparoscopic resection is increasingly being performed for rectal cancer. However, few data are available to compare long‐term outcomes after open versus laparoscopic surgery for early‐stage rectal cancer.

Methods

Included in this retrospective study were 160 patients who underwent surgery for stage I rectal cancer between 2001 and 2008. Perioperative outcomes, overall survival (OS), and disease‐free survival (DFS) were compared for open versus laparoscopic surgery.

Results

Altogether, 85 patients were treated using open surgery and 80 with laparoscopic surgery. Postoperative mortality (0 vs. 1.3 %; p = 1.00), morbidity (31.3 vs. 25.0 %; p = 0.38), and harvested lymph nodes (22.5 vs. 20.0; p = 0.84) were similar for the two groups. However, operating time was longer (183.8 vs. 221.0 min; p = 0.008), volume of intraoperative bleeding was less (200.0 vs. 150.0 ml; p = 0.03), time to first bowel movement was shorter (3.54 vs. 2.44 days; p < 0.001), rate of superficial surgical‐site infection was lower (7.5 vs. 0 %; p = 0.03), and postoperative hospital stay was shorter (11.0 vs. 8.0 days; p < 0.001) in the laparoscopy group than in the open surgery group. At 5 years, there was no difference in OS (98.6 vs. 97.1 %; p = 0.41) or DFS (98.2 vs. 96.4 %; p = 0.30) between the open and laparoscopy groups.

Conclusions

Long‐term outcomes of laparoscopic surgery for stage I rectal cancer were comparable to those of open surgery. Laparoscopic surgery, however, produced more favourable short‐term outcomes than open surgery.
The Prehospital Burden of Disease due to Trauma in KwaZulu‐Natal: The Need for Afrocentric Trauma Systems
Authors: Hardcastle Timothy Craig , Finlayson Melissa , van Heerden Marc , Johnson Ben , Samuel Candice , Muckart David J. J.
Published: November 2012

Background

Trauma is one of the leading prehospital disease profiles in South Africa in general and in KwaZulu‐Natal (KZN) in particular. The present study was designed to review the prehospital burden of injury in KZN, identify trauma burden to ambulance ratios, analyze system deficiencies, and propose a prehospital trauma system that is Afrocentric in nature.

Methods

Approval from the relevant ethics authorities was obtained. Using a convenience data set all Emergency Medical Service (EMS) call data for the months of March and September 2010 were reviewed for the three main EMS providers in KZN. Data were extrapolated to annual data and placed in the context of population, ambulance service, and facility. The data were then mapped for area distribution and prehospital workload relative to the entire province. Questionnaire‐based assessments of knowledge and deficiencies of the current system were completed by senior officers of the provincial system as part of the analysis of the current system.

Results

The total annual call burden for trauma ranges between 94,840 and 101,420, or around 11.6 trauma calls per thousand of the population per year. Almost 70 % of calls were either for interpersonal intentional violence or vehicular collisions. Only 0.25 % of calls involved aeromedical resources. Some 80 % of patients were considered to be moderately to seriously injured, yet only 41 % of the patients were transported to a suitable level of care immediately, with many going to inappropriate lower level care facilities. Many rural calls are not attended within the time norms accepted nationally. Deficiencies noted by the questionnaire survey are the general lack of a bypass mechanism and the feeling among staff that most EMS bases do not have a bypass option or feel part of a system of care, despite large numbers of staff having been recently trained in triage and major trauma care.

Conclusions

The prehospital trauma burden in KZN is significant and consumes vital resources and gridlocks facilities. A prehospital trauma system that is financially sustainable and meets the needs of the trauma burden is proposed to enable Afrocentric emergency care planning for low and middle income regions.
Anaesthesia and airway management in mucopolysaccharidosis
Authors: Walker Robert , Belani Kumar G. , Braunlin Elizabeth A. , Bruce Iain A. , Hack Henrik , Harmatz Paul R. , Jones Simon , Rowe Richard , Solanki Guirish A. , Valdemarsson Barbara
Published: November 2012

This paper provides a detailed overview and discussion of anaesthesia in patients with mucopolysaccharidosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical manifestations. The high prevalence of airway obstruction and restrictive pulmonary disease in combination with cardiovascular manifestations poses a high anaesthetic risk to these patients. Typical anaesthetic problems include airway obstruction after induction or extubation, intubation difficulties or failure [can't intubate, can't ventilate (CICV)], possible emergency tracheostomy and cardiovascular and cervical spine issues. Because of the high anaesthetic risk, the benefits of a procedure in patients with MPS should always be balanced against the associated risks. Therefore, careful evaluation of anaesthetic risk factors should be made before the procedure, involving evaluation of airways and cardiorespiratory and cervical spine problems. In addition, information on the specific type of MPS, prior history of anaesthesia, presence of cervical instability and range of motion of the temporomandibular joint are important and may be pivotal to prevent complications during anaesthesia. Knowledge of these risk factors allows the anaesthetist to anticipate potential problems that may arise during or after the procedure. Anaesthesia in MPS patients should be preferably done by an experienced (paediatric) anaesthetist, supported by a multidisciplinary team (ear, nose, throat surgeon and intensive care team), with access to all necessary equipment and support.
A Hierarchical Modeling Approach to Data Analysis and Study Design in a Multi-site Experimental fMRI Study
Authors: Zhou Bo , Konstorum Anna , Duong Thao , Tieu Kinh H. , Wells William M. , Brown Gregory G. , Stern Hal S. , Shahbaba Babak
Published: November 2012

We propose a hierarchical Bayesian model for analyzing multi-site experimental fMRI studies. Our method takes the hierarchical structure of the data (subjects are nested within sites, and there are multiple observations per subject) into account and allows for modeling between-site variation. Using posterior predictive model checking and model selection based on the deviance information criterion (DIC), we show that our model provides a good fit to the observed data by sharing information across the sites. We also propose a simple approach for evaluating the efficacy of the multi-site experiment by comparing the results to those that would be expected in hypothetical single-site experiments with the same sample size.
A Radiological Sign in Chronic Collateral Ligament Injuries of the Thumb Metacarpophalangeal Joint
Authors: Hunter Alistair R. , Tansey Rosamond J. , Muir Lindsay T.
Published: November 2012

Background

Differentiating chronic from acute injuries of the collateral ligament of the metacarpophalangeal joint (MCPJ) of the thumb can be difficult in the absence of a conclusive history and examination. We aimed to establish the presence of a radiological sign in patients with a chronic injury and the reliability of the sign in differentiating chronic from acute ligament injury.

Method

Consecutive patients undergoing surgical treatment for chronic ( n=14) or acute ( n=8) ligament injury of the MCPJ of the thumb were identified retrospectively. Six upper limb orthopedic surgeons and four musculoskeletal radiologists were recruited from three regional centers. Observers judged the presence or absence of the sign, an exostosis at the level of the neck of the thumb metacarpal, on radiographs presented on a computer program. The radiographs were then observed in a different random order. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of the radiological sign were evaluated for each observer and the intra- and interobserver error was calculated.

Results

The mean observer specificity and sensitivity for the sign were 84 and 54 %, respectively. The PPV and NPV were 89 and 52 %, respectively. The kappa statistic for intraobserver error was 0.69 and interobserver error 0.34. Conclusions A radiological sign associated with chronic collateral ligament injuries of the MCPJ of the thumb is established. The presence of the sign can increase the confidence of the clinician in differentiating chronic from acute collateral ligament injuries, when history and examination are inconclusive in this respect.
Factors Associated With Temporal and Spatial Patterns in Suicide Rates Across U.S. States, 1976–2000
Authors: Phillips Julie A.
Published: November 2012

Using pooled cross-sectional time-series data for the 50 U.S. states over a 25-year period, this article examines how well four conceptual groups of social correlates—demographic, economic, social, and cultural factors—are associated with the 1976–2000 patterns in overall suicide rates and suicide by firearms and other means. Unlike past research that typically considers only one dimension, this analysis differentiates between spatial and temporal variation in suicide rates to determine whether and how social correlates operate differently in these two contexts. Results indicate that suicide rates correspond closely to social correlates. Within U.S. states, lower overall suicide rates between 1976 and 2000 were associated with demographic change (e.g., larger numbers of foreign-born) as well as with fewer numbers of Episcopalians. Across U.S. states, variation in overall suicide rates over the period was related to demographic (percentage male), economic (per capita income), social (percentage divorced), and cultural (alcohol consumption and gun ownership) factors. However, findings differ importantly by type of suicide, and across time and space. Reasons for these distinct patterns are discussed.
Is Evil Good for Religion? The Link between Supernatural Evil and Religious Commitment
Authors: Martinez Brandon C.
Published: November 2012

“The devil made me do it” is a familiar cliché often used to justify a bad decision. However, are beliefs in a devil or other evil supernatural beings actually beneficial for religion? Building upon Stark and Bainbridge ( 1987 ) and elements of the supernatural punishment hypothesis, this study proposes and tests the hypothesis that a positive relationship exists between the belief in supernatural evil and religious commitment. Data from 2007 Baylor Religion Survey reveal a strong positive correlation between the belief in supernatural evil and four measures of religious commitment: church attendance, religious perception, tithing, and faith sharing. This study not only contributes to a long discussion of religious commitment, but it also has implications for the growing literature on god images and the supernatural punishment hypothesis.
AMPK mediates a pro‐survival autophagy downstream of PARP‐1 activation in response to DNA alkylating agents
Authors: Zhou Jing , Ng Shukie , Huang Qing , Wu You-Tong , Li Zhengqiu , Yao Shao Q. , Shen Han-Ming
Published: November 2012

In this study we aim to elucidate the signaling pathway and biological function of autophagy induced by MNNG, a commonly used DNA alkylating agent. We first observed that MNNG is able to induce necrotic cell death and autophagy in Bax−/− Bak−/− double knockout MEFs. We analyzed the critical role of PARP‐1 activation and ATP depletion in MNNG‐mediated cell death and autophagy via AMPK activation and mTOR suppression. We provide evidence that suppression of AMPK blocks MNNG‐induced autophagy and enhances cell death, suggesting the pro‐survival function of autophagy in MNNG‐treated cells. Taken together, data from this study reveal a novel mechanism in controlling MNNG‐mediated autophagy via AMPK activation downstream of PARP‐1 activation and ATP depletion.
14‐3‐3ɛ/ζ Affects the stability of δ‐catenin and regulates δ‐catenin‐induced dendrogenesis
Authors: He Yongfeng , Han Jeong Ran , Chang Ockyoung , Oh Minsoo , James Sarah E. , Lu Qun , Seo Young-Woo , Kim Hangun , Kim Kwonseop
Published: November 2012

Accumulated evidence suggests that aberrant regulation of δ‐catenin leads to pathological consequences such as mental retardation and cognitive dysfunction. This study revealed that 14‐3‐3ɛ/ζ stabilizes δ‐catenin, with different binding regions involved in the interaction. Furthermore, the specific inhibition of the interaction of 14‐3‐3 with δ‐catenin reduced levels of δ‐catenin and significantly impaired the capacity of δ‐catenin to induce dendritic branching in both NIH3T3 fibroblasts and primary hippocampal neurons. However, the S1094A δ‐catenin mutant, which cannot interact with 14‐3‐3ζ, still retained the capability of inducing dendrogenesis. Taken together, these results elucidate the underlying events that regulate the stability of δ‐catenin and δ‐catenin‐induced dendrogenesis.
A case–control study of placental lesions associated with pre‐eclampsia
Authors: Devisme Louise , Merlot Benjamin , Ego Anne , Houfflin‐Debarge Veronique , Deruelle Philippe , Subtil Damien
Published: November 2012

Objective

To investigate gross and microscopic placental lesions associated with pre‐eclampsia and to determine which lesions are most strongly linked to serious pregnancy complications.

Methods

A retrospective case–control study of 173 placentas from women with pre‐eclampsia and 173 placentas from healthy normotensive women was conducted.

Results

The mean placental weight in the pre‐eclampsia group was lower than that recorded for the control group (280 g vs 360 g; P < 0.001). Infarcts (65.9% vs 13.2%; P < 0.001) and placental abruption (P < 0.001) were most frequent among women with pre‐eclampsia. Microscopic findings showed the following lesions to be associated with pre‐eclampsia: hypermature villi, defined by absence of intermediate villi (72% vs 16%; P < 0.001), excessive syncytial knots (90% vs 9%; P < 0.001), decidual vasculopathy (51% vs 8%; P < 0.001), villous fibrosis (6% vs 0%; P < 0.001), erythroblastosis (11% vs 4%; P < 0.01), and avascular terminal villi (9% vs 3%; P < 0.05). Increased syncytial knots, infarcts, basal decidual vasculopathy, hypermature villi, and placental erythroblastosis were still associated with pre‐eclampsia after logistic regression modeling.

Conclusion

Placental lesions most strongly associated with pre‐eclampsia were all causes or expressions of placental hypoxia or ischemia, which appears as the primary mechanism of pre‐eclampsia.
Bone metastasis versus bone marrow metastasis? Integration of diagnosis by 18F‐fluorodeoxyglucose positron emission/computed tomography in advanced malignancy with super bone scan: Two case reports and literature review
Authors: Lin Chia‐Yang , Chen Yu‐Wen , Chang Chin‐Chuan , Yang Wen‐Chi , Huang Chih‐Jen , Hou Ming‐Feng
Published: November 2012

Super scan pattern on technetium‐99m methyldiphosphonate (Tc‐99m MDP) bone scintigraphy is a special condition of extremely high bone uptake relative to soft tissue with absent or faint renal radioactivity visualization, which is usually seen in diffuse bone metastases or discrete endocrine entities. Here, two cases with super bone scan are presented. One was a young man diagnosed with gastric cancer. The other was a middle‐aged woman with a history of breast cancer with recent recurrence. Both cases had 18‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) diagnosis simultaneously. Based on imaging of 18F‐FDG PET/CT, diffusely incremental 18F‐FDG avidity in spine/pelvis on PET and subtle erosion of cortical bone on CT were seen. The cytological results of bone marrow biopsy showed evidence of malignant metastasis. However, there were several focal discrepant findings between the 18F‐FDG PET/CT and Tc‐99m MDP bone scan. According to integration of both imaging findings and the result of bone marrow biopsy, we believe that the disseminated malignant spread in bone marrow is a primitive alternation in the super bone scan and that it is also as a result of neoplasm‐related endocrine factors.
FLT3 signals via the adapter protein Grb10 and overexpression of Grb10 leads to aberrant cell proliferation in acute myeloid leukemia
Authors: Kazi Julhash U. , Rönnstrand Lars
Published: November 2012

The adaptor protein Grb10 plays important roles in mitogenic signaling. However, its roles in acute myeloid leukemia (AML) are predominantly unknown. Here we describe the role of Grb10 in FLT3‐ITD‐mediated AML. We observed that Grb10 physically associates with FLT3 in response to FLT3‐ligand (FL) stimulation through FLT3 phospho‐tyrosine 572 and 793 residues and constitutively associates with oncogenic FLT3‐ITD. Furthermore endogenous Grb10–FLT3 association was observed in OCI‐AML‐5 cells. Grb10 expression did not alter FLT3 receptor activation or stability in Ba/F3‐FLT3 cells. However, expression of Grb10 enhanced FL‐induced Akt phosphorylation without affecting Erk or p38 phosphorylation in Ba/F3‐FLT3‐WT and Ba/F3‐FLT3‐ITD. Selective Grb10 depletion reduced Akt phosphorylation in Ba/F3‐FLT3‐WT and OCI‐AML‐5 cells. Grb10 transduces signal from FLT3 by direct interaction with p85 and Ba/F3‐FLT3‐ITD cells expressing Grb10 exhibits higher STAT5 activation. Grb10 regulates the cell cycle by increasing cell population in S‐phase. Expression of Grb10 furthermore resulted in an increased proliferation and survival of Ba/F3‐FLT3‐ITD cells as well as increased colony formation in semisolid culture. Grb10 expression was significantly increased in AML patients compared to healthy controls and was also elevated in patients carrying FLT3‐ITD mutants. The elevated Grb10 expression partially correlated to relapse as well as to poor prognosis. These results suggest that Grb10 binds to both normal and oncogenic FLT3 and induces PI3K–Akt and STAT5 signaling pathways resulting in an enhanced proliferation, survival and colony formation of hematopoietic cells.
STIT tessellations are Bernoulli and standard
Authors: MARTÍNEZ SERVET
Published: November 2012

Let (Yt:t>0) be a STIT tessellation process and a>1. We prove that the random sequence (anYan:n∈ℤ) is a non-anticipating factor of a Bernoulli shift. We deduce that the continuous time process (atYat:t∈ℝ) is a Bernoulli flow. We use the techniques and results in Martínez and Nagel [Ergodic description of STIT tessellations. Stochastics 84(1) (2012), 113–134]. We also show that the filtration associated to the non-anticipating factor is standard in Vershik’s sense.
Dietary patterns among Norwegian 2-year-olds in 1999 and in 2007 and associations with child and parent characteristics
Authors: Kristiansen Anne Lene , Lande Britt , Sexton Joseph Andrew , Andersen Lene Frost
Published: November 2012

Infant and childhood nutrition influences short- and long-term health. The objective of the present paper has been to explore dietary patterns and their associations with child and parent characteristics at two time points. Parents of Norwegian 2-year-olds were, in 1999 (n 3000) and in 2007 (n 2984), invited to participate in a national dietary survey. At both time points, diet was assessed by a semi-quantitative FFQ that also provided information on several child and parent characteristics. A total of 1373 participants in the 1999 sample and 1472 participants in the 2007 sample were included in the analyses. Dietary patterns were identified by principal components analysis and related to child and parent characteristics using the general linear model. Four dietary patterns were identified at each time point. The ‘unhealthy’ and ‘healthy’ patterns in 1999 and 2007 showed similarities with regard to loadings of food groups. Both the ‘bread and spread-based’ pattern in 1999 and the ‘traditional’ pattern in 2007 had high positive loadings for bread and spreads; however, the ‘traditional’ pattern did also include positive associations with a warm meal. The last patterns identified in 1999 and in 2007 were not comparable with regard to loadings of food groups. All dietary patterns were significantly associated with one or several child and parent characteristics. In conclusion, the ‘unhealthy’ patterns in 1999 and in 2007 showed similarities with regard to loadings of food groups and were, at both time points, associated with sex, breastfeeding at 12 months of age, parity, maternal age and maternal work situation.
Using APSIM to explore wheat yield response to climate change in the North China Plain: the predicted adaptation of wheat cultivar types to vernalization
Authors: ZHANG Y. , FENG L. P. , WANG J. , WANG E. L. , XU Y. L.
Published: November 2012

Cultivar selection is a dominant factor in crop production to obtain high yield. While previous studies have evaluated a range of impacts and adaptation of climate change (CC) on crop yield, few studies have focused on evaluating the effectiveness of changing cultivars with different vernalization requirements as an adaptation. In the present study, mean and inter-annual variability of yield were quantified for three winter wheat cultivar types at three ecological sites (Shangzhuang in Beijing, Quzhou in Hebei and Huangfanqu in Henan) in the North China Plain, by linking a crop model and the outputs of Providing Regional Climates for Impacts Studies (PRECIS) for both the baseline (1961–90) and future SRES scenarios A2 and B2 (2070–2100). The results showed that a warming trend prolonged the length of the vegetative growth period of local cultivars through reduced vernalization, generally leading to a negative impact on yield. However, the introduction of cultivars with relatively lower vernalization demands from warmer southern to cooler northern regions could be an effective adaptation strategy to offset the negative impact of climatic change. Adjustment in cultivars increased yield at Shangzhuang and maintained it at Quzhou and Huangfanqu. Elevated CO2would significantly increase yield in the future with or without considering the sensitivities of the selected cultivars. The inter-annual variability of yield generally increased in the A2 scenario, but decreased in the B2 scenario. Overall, winter wheat with semi-winter types or weak-winter types would grow preferentially, while cultivars with winter types would probably be reduced in future.
DISTINGUISHING THE IMPACT OF POSTPONEMENT, SPACING AND STOPPING ON BIRTH INTERVALS: EVIDENCE FROM A MODEL WITH HETEROGENEOUS FECUNDITY
Authors: TIMÆUS IAN M. , MOULTRIE TOM A.
Published: November 2012

This paper investigates the impact on birth intervals of three distinct birth control strategies: stopping childbearing, spacing births and the postponement of further childbearing for reasons unrelated to women's family-building histories. A macro-simulation model of the family-building process is described that incorporates heterogeneity in fecundability. This model is used to demonstrate that the postponement of further childbearing has a distinctive impact on schedules of duration-specific fertility rates that differs from that of both family-size limitation and birth spacing. In particular, the simulation results, supplemented by an analytical exposition, show that reductions in fertility due to spacing are a function of interval duration and its log, while reductions due to postponement are a function of interval duration and its square. This provides a way to test statistically for the presence of, and distinguish between, differential postponement and spacing in regression analyses of birth history data.
Cognitive Dissonance, Sentiment, and Momentum
Authors: Antoniou Constantinos , Doukas John A. , Subrahmanyam Avanidhar
Published: November 2012

We consider whether sentiment affects the profitability of momentum strategies. We hypothesize that news that contradicts investors’ sentiment causes cognitive dissonance, slowing the diffusion of such news. Thus, losers (winners) become underpriced under optimism (pessimism). Short-selling constraints may impede arbitraging of losers and thus strengthen momentum during optimistic periods. Supporting this notion, we empirically show that momentum profits arise only under optimism. An analysis of net order flows from small and large trades indicates that small investors are slow to sell losers during optimistic periods. Momentum-based hedge portfolios formed during optimistic periods experience long-run reversals.
Striking the right balance: issues of transition for the beginner secondary music teacher
Authors: Cyster Drew
Published: November 2012

Transition from primary to secondary school in the UK has received considerable attention in educational research over the last few decades, although specific focus on transition in music has only been relatively recently addressed. Research by Mills (1996) and Marshall and Hargreaves (2007, 2008) draws upon both general and music-specific studies to provide insights into the educational value of common transition practices for pupils and teachers. While evidence from the recent surveys indicate significant progress in promoting successful transitions compared with earlier research, there continue to be areas requiring further enquiry, particularly that of curriculum progression and pupil achievement in music.
Editorial
Authors: BURNARD PAMELA , SPRUCE GARY
Published: November 2012

This is a rather different Editorial. It marks the end of five years of editorship. So, a few valedictory remarks will begin and end this piece. When we first took over co-editing the British Journal of Music Education in 2007–2008, from the distinguished editorship of Stephanie Pitts and Gordon Cox, we introduced ourselves alongside contributing authors in the editorial for Volume 25 with articles in a series tackling the contribution of music education research and theory to practice and so signalled our intention as an editorial team to strengthen further the remit of the journal. In this Volume 29, four years on, we feel very pleased to report a significant increase in submissions to the British Journal of Music Education and a welcome further internationalisation of contributions. We now web publish and feature teacher-researcher and school-based research in each issue. The British Journal of Music Education is now featured in the Thomson Reuters Arts & Humanities Citation Index and the Social Science Citation Index. We both feel privileged to have been given the opportunity of working for this highly regarded journal whose reputation has continued to grow and strive to strengthen connections between research and practice, and offer informed and passionate engagement with music education research for empowerment and advocacy.
Changing epidemiology of methicillin-resistantStaphylococcus aureuscolonization in paediatric intensive-care units
Authors: HERMOS C. R. , SANDORA T. J. , WILLIAMS L. E. , MOSAMMAPARAST N. , McADAM A. J.
Published: November 2012

Community-associated methicillin-resistantS. aureus(CA-MRSA) accounts for a growing proportion of hospital-onset infections, and colonization is a risk factor. This study aimed to determine changes in the prevalence of CA-MRSA colonization in paediatric intensive-care units (ICUs). A total of 495 paediatric patients colonized with MRSA from neonatal, medical, surgical, and cardiac ICUs between 2001 and 2009 were identified. Isolates were characterized byspatype, staphylococcal cassette chromosome (SCC)mectype and the presence of the genes encoding Panton–Valentine leukocidin (PVL). The proportion of patients colonized with MRSA remained stable (average 3·2%). The proportion of isolates withspatype 1, SCCmectype IV and PVL increased over time to maximums in 2009 of 36·1% (P < 0·001), 54·2% (P = 0·03) and 28·9% (P = 0·003), respectively. Antibiotic susceptibility patterns showed increasing proportions susceptible to clindamycin, gentamicin, tetracycline and trimethoprim-sulfamethoxazole (Pvalues <0·001). In conclusion, the proportion of MRSA-colonized children in ICUs with CA-MRSA increased significantly over time.
Correspondence between genetic structure and farmers' taxonomy – a case study from dry-season sorghum landraces in northern Cameroon
Authors: Soler Clelia , Saidou Abdoul-Aziz , Vi Cao Hamadou Tuong , Pautasso Marco , Wencelius Jean , Joly Hélène H. I.
Published: November 2012

The study of the genetic structure of cultivated plant populations maintained by farmers is of great importance for evolutionary and conservation biology. Such studies help understand the bases of crop evolution and conservation in relation to farmers' practices. In this study, we assessed the genetic structure underlying landrace diversity of dry-season sorghum. This crop constitutes a historical model of innovation developed by farmers to extend sorghum cultivation to the dry season. Two types of dry-season sorghum are cultivated. We aimed to assess the link between farmers' taxonomy and molecular genetic structure. We collected both types of dry-season sorghum in two villages of northern Cameroon which represented 20 landraces. These landraces were genotyped using eight polymorphic microsatellite markers. This study compared two clustering methods: a Bayesian method (STRUCTURE) which is based on explicit genetic assumptions and the discriminant analysis of principal component method. The latter, more recently proposed, is based on the combination of principal component analysis and discriminant analysis. We noticed a general congruence between these two methods. We also used both methods to infer the genetic structure of our sample. Our results showed strong genetic structuring of the landraces, withK= 14 genetic clusters. We then analysed the fit between farmers' taxonomy and genetic structure. The data suggested that each type and each landrace corresponds to a given genetic entity. This pattern was robust across both villages, despite differences in cultural practices.
Molecular distinction of two closely resembling Morinda species using rbcL and matK loci for quality management of Indian herbal medicines
Authors: Nair Rahul R. , Udayan P. S. , Thilaga S. , Kavitha M. , Bharathanandhini R. M. , Nizzy A. M. , Ganesh D.
Published: November 2012

Morinda reticulata Gamble and Morinda umbellata Linn. (Rubiaceae) are medicinally important climbers distributed as a mixed population in southern Western Ghats of India. A close morphological resemblance of these two species misleads the harvester in the identification of plant parts for preparation of herbal medicines. Though both species contain anthraquinone derivatives and share common medicinal properties for treating stomach disorders, each of these species has unique curative properties for treating selective diseases. Conventional methods are not reliable for identification of these species due to similarities in morphology. Thus, misidentification often leads to the deterioration of the quality of medicines. Thus, authentication utilizing conserved gene sequences in the chloroplast genome of these two Morinda spp. has been attempted for precise identification. Here we report the use of two barcoding genes (maturase kinase and ribulose 1,5-bisphosphate carboxylase large subunit) to distinguish M. reticulata and M. umbellata based on single nucleotide polymorphism. The present findings can be used for authenticating leaf samples of M. reticulata and M. umbellata.
Simulation of the seeding of equatorial spread F by circular gravity waves
Authors: Krall J. , Huba J. D. , Joyce G. , Hei Matthew
Published: November 2012

The Naval Research Laboratory three‐dimensional simulation code SAMI3/ESF is used to study the response of the postsunset ionosphere to circular gravity waves. We model the coupling of both circular (local) and plane wave (nonlocal) gravity waves to the bottomside F layer as a mechanism for triggering equatorial plasma bubbles. Results support the hypothesis that nonplane gravity waves can more strongly couple to the F layer than plane gravity waves. Results also show that the coupling of the seed wave to the F layer depends on the (nonlocal) growth rate and the local electron density at the position of the seed wave.
Modeling the plasmasphere with SAMI3
Authors: Huba J. , Krall J.
Published: November 2012

The study of the plasmasphere is extremely important to understanding space weather phenomena; for example, it plays a critical role in the regulation of radiation belt dynamics. In this paper, the first 3D simulation of the plasmasphere based on the first‐principles physics model SAMI3 is presented. We include the co‐rotation potential, the neutral wind dynamo potential, and a time‐dependent Volland‐Stern‐Maynard‐Chen potential to model the response of the convection potential to an idealized magnetic storm. We find that prior to the storm the plasmasphere is largely toroidal and symmetric in magnetic local time with He+/H+ ~ 5–10%. After the storm, the plasmasphere substantially contracts because plasma is convected away from the outer plasmasphere by the enhanced convection velocity. Moreover, a plume‐like structure forms in the mid‐afternoon sector because of the modified convection pattern associated with the storm. Additionally good agreement is found between the simulation results and data for the L‐shell dependence of the equatorial electron density as well as the electron density along the field line at a given L‐shell under quiet geomagnetic conditions.
Three‐dimensional, impulsive magnetic reconnection in a laboratory plasma
Authors: Dorfman S. , Ji H. , Yamada M. , Yoo J. , Lawrence E. , Myers C. , Tharp T. D.
Published: November 2012

Impulsive, local, 3‐D reconnection is identified for the first time in a laboratory current sheet. The events observed in the Magnetic Reconnection Experiment are characterized by large local gradients in the third direction and cannot be explained by 2‐D models. Detailed measurements show that the ejection of flux rope structures from the current sheet plays a key role in these events. By contrast, even though electromagnetic fluctuations in the lower hybrid frequency range are also observed concurrently with the impulsive behavior, they are not the key physics responsible. A qualitative, 3‐D, two‐fluid model is proposed to explain the observations. The experimental results may be particularly applicable to space and astrophysical plasmas where impulsive reconnection occurs.
Uncertainties and importance of sea spray composition on aerosol direct and indirect effects
Authors: Tsigaridis Kostas , Koch Dorothy , Menon Surabi
Published: November 2012

Although ocean‐derived aerosols play a critical role in modifying the radiative balance over much of the Earth, their sources are still subject to large uncertainties, concerning not only their total mass flux but also their size distribution and chemical composition. These uncertainties are linked primarily to their source drivers, which is mainly wind speed, but are also linked to other factors, such as the presence of organic compounds in sea spray in addition to sea salt. In order to quantify these uncertainties and identify the larger knowledge gaps, we performed several model runs with online calculation of aerosol sources, removal, and underlying climate. In these simulations, both the direct and indirect aerosol effects on climate are included. The oceanic source of organic aerosols was found to be heavily dependent on the sea‐salt parameterization selected. For only a factor of 2 change in assumed fine‐mode sea‐salt size, a factor of 10 difference in mass emissions was calculated for both sea salt and primary oceanic organics. The annual emissions of oceanic organics were calculated to range from 7.5 to 76 Tg yr‐1. The model's performance against remote oceanic measurements was greatly improved when including the high estimates of organics. However, the uncertainty could not be further reduced by bulk sea‐salt measurements alone since most parameterizations tested agree reasonably well with measurements of both the (coarse‐mode‐dominated) sea salt and aerosol optical depth due to large changes in lifetime and optical properties of aerosols when different aerosol sizes are used.