bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Narrative Evidence and Explicit Likelihood by Decisionmakers Varying in Numeracy
Authors: Dieckmann Nathan F. , Slovic Paul , Peters Ellen M.
Published: August 2009

Decisionmakers are often presented with explicit likelihood assessments (e.g., there is a 10% chance that an attack will occur over the next three months) and supporting narrative evidence in forecasting and risk communication domains. Decisionmakers are thought to rely on both numerical and narrative information to the extent that they perceive the information to be diagnostic, accurate, and trustworthy. In two studies, we explored how lay decisionmakers varying in numeracy evaluated and used likelihood assessments and narrative evidence in forecasts. Overall, the less numerate reported higher risk and likelihood perceptions. In simple probabilistic forecasts without narrative evidence, decisionmakers at all levels of numeracy were able to use the stated likelihood information, although risk perceptions of the less numerate were more affected by likelihood format. When a forecast includes narrative evidence, decisionmakers were better able to use stated likelihood in a percentage as compared to frequency or verbal formats. The more numerate used stated likelihood more in their evaluations whereas the less numerate focused more on the narrative evidence. These results have important implications for risk analysts and forecasters who need to report the results of their analyses to decisionmakers. Decisionmakers varying in numerical ability may evaluate forecasts in different ways depending on the types of information they find easiest to evaluate.
Improving the Predictive Accuracy of Hurricane Power Outage Forecasts Using Generalized Additive Models
Authors: Han Seung‐Ryong , Guikema Seth D. , Quiring Steven M.
Published: August 2009

Electric power is a critical infrastructure service after hurricanes, and rapid restoration of electric power is important in order to minimize losses in the impacted areas. However, rapid restoration of electric power after a hurricane depends on obtaining the necessary resources, primarily repair crews and materials, before the hurricane makes landfall and then appropriately deploying these resources as soon as possible after the hurricane. This, in turn, depends on having sound estimates of both the overall severity of the storm and the relative risk of power outages in different areas. Past studies have developed statistical, regression‐based approaches for estimating the number of power outages in advance of an approaching hurricane. However, these approaches have either not been applicable for future events or have had lower predictive accuracy than desired. This article shows that a different type of regression model, a generalized additive model (GAM), can outperform the types of models used previously. This is done by developing and validating a GAM based on power outage data during past hurricanes in the Gulf Coast region and comparing the results from this model to the previously used generalized linear models.
Utility‐Based Optimization of Combination Therapy Using Ordinal Toxicity and Efficacy in Phase I/II Trials
Authors: Houede Nadine , Thall Peter F. , Nguyen Hoang , Paoletti Xavier , Kramar Andrew
Published: August 2009

Summary An outcome‐adaptive Bayesian design is proposed for choosing the optimal dose pair of a chemotherapeutic agent and a biological agent used in combination in a phase I/II clinical trial. Patient outcome is characterized as a vector of two ordinal variables accounting for toxicity and treatment efficacy. A generalization of the Aranda‐Ordaz model (1981, Biometrika 68, 357–363) is used for the marginal outcome probabilities as functions of a dose pair, and a Gaussian copula is assumed to obtain joint distributions. Numerical utilities of all elementary patient outcomes, allowing the possibility that efficacy is inevaluable due to severe toxicity, are obtained using an elicitation method aimed to establish consensus among the physicians planning the trial. For each successive patient cohort, a dose pair is chosen to maximize the posterior mean utility. The method is illustrated by a trial in bladder cancer, including simulation studies of the method's sensitivity to prior parameters, the numerical utilities, correlation between the outcomes, sample size, cohort size, and starting dose pair.
A Bayesian Approach to Surrogacy Assessment Using Principal Stratification in Clinical Trials
Authors: Li Yun , Taylor Jeremy M.G. , Elliott Michael R.
Published: August 2009

Summary A surrogate marker (S) is a variable that can be measured earlier and often more easily than the true endpoint (T) in a clinical trial. Most previous research has been devoted to developing surrogacy measures to quantify how well S can replace T or examining the use of S in predicting the effect of a treatment (Z). However, the research often requires one to fit models for the distribution of T given S and Z. It is well known that such models do not have causal interpretations because the models condition on a postrandomization variable S. In this article, we directly model the relationship among T, S, and Z using a potential outcomes framework introduced by Frangakis and Rubin (2002, Biometrics 58, 21–29). We propose a Bayesian estimation method to evaluate the causal probabilities associated with the cross‐classification of the potential outcomes of S and T when S and T are both binary. We use a log‐linear model to directly model the association between the potential outcomes of S and T through the odds ratios. The quantities derived from this approach always have causal interpretations. However, this causal model is not identifiable from the data without additional assumptions. To reduce the nonidentifiability problem and increase the precision of statistical inferences, we assume monotonicity and incorporate prior belief that is plausible in the surrogate context by using prior distributions. We also explore the relationship among the surrogacy measures based on traditional models and this counterfactual model. The method is applied to the data from a glaucoma treatment study.
Semiparametric Bayesian Analysis of Nutritional Epidemiology Data in the Presence of Measurement Error
Authors: Sinha Samiran , Mallick Bani K. , Kipnis Victor , Carroll Raymond J.
Published: August 2009

Summary: We propose a semiparametric Bayesian method for handling measurement error in nutritional epidemiological data. Our goal is to estimate nonparametrically the form of association between a disease and exposure variable while the true values of the exposure are never observed. Motivated by nutritional epidemiological data, we consider the setting where a surrogate covariate is recorded in the primary data, and a calibration data set contains information on the surrogate variable and repeated measurements of an unbiased instrumental variable of the true exposure. We develop a flexible Bayesian method where not only is the relationship between the disease and exposure variable treated semiparametrically, but also the relationship between the surrogate and the true exposure is modeled semiparametrically. The two nonparametric functions are modeled simultaneously via B‐splines. In addition, we model the distribution of the exposure variable as a Dirichlet process mixture of normal distributions, thus making its modeling essentially nonparametric and placing this work into the context of functional measurement error modeling. We apply our method to the NIH‐AARP Diet and Health Study and examine its performance in a simulation study.
Some Historical Conditions of Narrative Work
Authors: BEELS C. CHRISTIAN
Published: August 2009

Written to honor the immense contribution of Michael White as a leader in the development of narrative therapy, this historical essay contrasts the origins of psychoanalysis, family therapy and narrative therapy. Changes in the understanding of therapeutic strategies, methods of training and supervision, styles of leadership, the involvement of audiences in the therapeutic and training processes, and conceptions of the nature of the mind are described. A style of direct demonstration of methods, especially of the formulation of questions, is important in narrative work. The central master‐role of the therapist in analysis and family therapy is replaced in narrative work by eliciting local knowledge, and the recruitment of audiences to the work. This is consistent with narrative therapy's “de‐centered” image of the therapist.
Couples with Schizophrenia “Becoming like Others” in South Korea: Marriage as Part of a Recovery Process
Authors: YU MYUNG‐YEE , SHIM WOOCHAN
Published: August 2009

Very little is known about the married life of couples with schizophrenia. In this paper, authors report perceptions and experiences of 5 married couples with schizophrenia on their strategies in forming and maintaining healthy marriage. Our data reveal that participants had realistic expectations of marriage, and recognized benefits as well as obstacles in their marriages with respect to their recovery. This paper examines the importance of extended family members, mental health professionals, and the larger society's attitudes toward marriage as a factor in the recovery process for persons with schizophrenia. The authors identify implications for mental health professionals regarding the respect of client dignity and the applicability of a strengths perspective when working with couples with schizophrenia. The authors argue that mental health professionals' decisions regarding the balance between respecting a client's self‐determination and protecting a client from risks associated with cohabitation and marriage should no longer be a dilemma for those working with people with mental illness.
How Adolescent Children of African Jamaican Immigrants Living in Canada Perceive and Negotiate their Roles within a Matrifocal Family
Authors: NAVARA GEOFFREY S. , LOLLIS SUSAN
Published: August 2009

This research project examined the adolescent/young adult‐parent relationships of African Jamaican immigrants currently living in Canada. Specifically, we focused on the transmission of cultural values and beliefs within these relationships and how the adolescents navigated and negotiated potential changes in these values because of their acculturative experiences. An examination of various mundane family/cultural practices provided insight into perceived transmission attempts by parents and the adolescent/young adult interpretation of these attempts. Twenty in‐depth interviews were conducted with adolescent/young adult members of African Jamaican immigrant families living in Canada. Using Grounded Theory methodology (Glaser & Strauss, 1967), several themes emerged during the analysis of the interviews—the most significant being the issue of matrifocality within the African Jamaican family. Issues of respect and adolescent agency are also discussed as they related to the manner in which the adolescent/young adult attempted to negotiate various roles within the family.
Effect of Trainees on Length of Stay in the Pediatric Emergency Department
Authors: James Catherine , Harper Marvin , Johnston Patrick , Sanders Brian , Shannon Michael
Published: August 2009

Background:  Emergency departments (EDs) in teaching hospitals have competing goals of timely patient care and supervised trainee education. Previous investigations have indicated that trainees add time to the length of ED patient encounters. However, no studies have quantified the effect of trainees on pediatric ED length of stay (LOS).

Objectives:  The objectives were to measure the effect of trainees on pediatric ED LOS by comparing LOS for patients managed by a pediatric emergency physician (PEP) alone to LOS for patients seen by a trainee and a precepting PEP (Trainee+PEP). A secondary objective was to identify factors other than provider type associated with LOS differences observed in teaching hospital pediatric EDs.

Methods:  Data were extracted from a computerized ED tracking system in an urban tertiary care children’s hospital with approximately 52,000 visits annually. All patients were seen by a PEP alone, an urgent care physician, or a trainee (a pediatric emergency medicine fellow; a pediatric, emergency medicine, or combined internal medicine/pediatrics resident; or a medical student) plus a precepting PEP. The primary comparison was the ratio of median LOS for the PEP group versus the Trainee+PEP group.

Results:  There were 92,193 visits eligible for inclusion over a 2‐year period. Median patient age was 5.75 years (interquartile range [IQR] = 21 months to 12.9 years). The PEP group managed 9,141 patients (10%), while the Trainee+PEP group treated 72,135 patients (78%). Overall LOS for an ED visit was 221 minutes. The median LOS was 192 minutes for PEP patients and 225 minutes for Trainee+PEP patients (difference of means = 17%, p < 0.001). Laboratory and imaging studies were associated with LOS increases of 111 and 74 minutes, respectively; both were performed more frequently in Trainee+PEP patients (44% vs. 33% for laboratory studies and 41% vs. 39% for imaging studies, both comparisons p < 0.001). When LOS was analyzed after adjusting for confounding factors including patient acuity, laboratory or radiologic testing, and trainee year, LOS for Trainee+PEP was higher by 17 minutes, or 9% (95% confidence interval [CI] = 6% to 12%, p < 0.001). When LOS was examined for four specific diagnoses (asthma, gastroenteritis, appendicitis, foot/ankle sprain), there were no significant differences in LOS between the PEP and Trainee+PEP groups.

Conclusions:  In the pediatric ED of a teaching hospital, ED LOS is on average 9% higher in patients seen by trainees. In an era of increasing efforts to accelerate throughput while training future providers, these findings provide an important metric for the delivery of pediatric emergency care.
Antiapoptotic Cardioprotective Effect of Hypothermia Treatment Against Oxidative Stress Injuries
Authors: Huang Chien‐Hua , Chen Huei‐Wen , Tsai Min‐Shan , Hsu Chiung‐Yuan , Peng Ren‐How , Wang Tzung‐Dau , Chang Wei‐Tien , Chen Wen‐Jone
Published: August 2009

Objectives:  The effect of hypothermia on cardiomyocyte injury induced by oxidative stress remains unclear. The authors investigated the effects of hypothermia on apoptosis and mitochondrial dysfunction in cardiomyocytes exposed to oxidative stress.

Methods:  Cardiomyocytes (H9c2) derived from embryonic rat heart cell culture were exposed to either normothermic (37°C) or hypothermic (31°C) environments before undergoing oxidative stress via treatment with hydrogen peroxide (H2O2). The degree of apoptosis was determined by annexin V and terminal deoxynucleotidyl transferase (TUNEL) staining. The amount of reactive oxygen species (ROS) was compared after H2O2 exposure between normo‐ and hypothermic‐pretreated groups. Mitochondrial dysfunction in both groups was measured by differential reductase activity and transmembrane potential (ΔΨm).

Results:  Hydrogen peroxide induced significant apoptosis in both normothermic and hypothermic cardiomyocytes. Hypothermia ameliorated apoptosis as demonstrated by decreased annexin V staining (33 ± 1% vs. 49 ± 4%; p < 0.05) and TUNEL staining (27 ± 17% vs. 80 ±25%; p < 0.01). The amount of intracellular ROS increased after H2O2 treatment and was higher in the hypothermic group than that in the normothermic group (237.9 ± 31.0% vs. 146.6 ± 20.6%; p < 0.05). In the hypothermic group, compared with the normothermic group, after H2O2 treatment mitochondrial reductase activity was greater (72.0 ± 17.9% vs. 27.0 ± 13.3%; p < 0.01) and the mitochondria ΔΨm was higher (101.0 ± 22.6% vs. 69.7 ± 12.9%; p < 0.05). Pretreatment of cardiomyocytes with the antioxidant ascorbic acid diminished the hypothermia‐induced increase in intracellular ROS and prevented the beneficial effects of hypothermia on apoptosis and mitochondrial function.

Conclusions:  Hypothermia at 31°C can protect cardiomyocytes against oxidative stress–induced injury by decreasing apoptosis and mitochondrial dysfunction through intracellular ROS‐dependent pathways.
Randomized Double‐blind Placebo Controlled Crossover Study of Acetaminophen, Ibuprofen, Acetaminophen/Hydrocodone, and Placebo for the Relief of Pain From a Standard Painful Stimulus
Authors: Miner James R.
Published: August 2009

Objectives:  The objective was to compare subjects’ change in perceived acute pain from an identical painful stimulus after receiving three separate, commonly used pain medications and placebo.

Methods:  This was an institutional review board–approved, randomized, double‐blind crossover study of healthy human volunteers. Subjects received 1000 mg of acetaminophen, 800 mg of ibuprofen, the combination of 650 mg of acetaminophen with 10 mg of hydrocodone, or placebo (800 mg of lactose) in a randomized order over four separate occasions each 1 week apart. Prior to receiving the drug on each study day, subjects placed their nondominant hand in a bath of 0°C water for 45 seconds. The bath was divided into two sections; the larger was the reservoir of cooled water monitored at 0°C, and the other half was filled from constant overflow. Water drained from the overflow section into the cooling unit and was then pumped up into the base of the reservoir through a diffusion grid. Subjects completed a 100‐mm visual analog scale (VAS) representing perceived pain during the exposure. The cold water exposure and VAS were repeated 1 hour after receiving the study drug, and then subjects were observed for side effects for 4 hours. Data were compared using descriptive statistics, 95% confidence intervals (CIs), and repeated‐measures analysis of variance (ANOVA).

Results:  Twenty‐five subjects were enrolled. The mean VAS preexposure was 56.9 mm (±15.1 mm; range = 5 to 92 mm). The mean decrease in VAS after receiving the study drug for acetaminophen was 10.2% (95% CI = −1.4 to 20.4), for ibuprofen was −6.6% (95% CI = −16.5 to 3.20), for acetaminophen/hydrocodone was 9.5% (95% CI = 1.4 to 20.4), and for placebo was −6.9% (95% CI = −15.2 to 1.4). The range in change in pain scores for all agents was −91.3% to 57.6%. Mild side effects (nausea, dizziness, or somnolence) were reported in 11 subjects (44%) after receiving acetaminophen/hydrocodone; no other side effects were reported.

Conclusions:  There was a wide range of changes in pain scores from this identical painful stimulus after receiving the study medications. Acetaminophen and acetaminophen/hydrocodone resulted in a similar decrease in pain (10.2 and 9.5%), while ibuprofen and placebo had a similar lack of effect (−6.6 and −6.9%). Forty‐four percent of subjects receiving acetaminophen/hydrocodone reported mild side effects; no other side effects were seen. In this noninflammatory pain model, the VAS is not able to distinguish differences in pain relief between acetaminophen and acetaminophen/hydrocodone or ibuprofen and placebo.
Combined Residency Training in Emergency Medicine and Internal Medicine: An Update on Career Outcomes and Job Satisfaction
Authors: Kessler Chad S. , Stallings Leonard A. , Gonzalez Andrew A. , Templeman Todd A.
Published: August 2009

Objectives:  This study was designed to provide an update on the career outcomes and experiences of graduates of combined emergency medicine‐internal medicine (EM‐IM) residency programs.

Methods:  The graduates of the American Board of Emergency Medicine (ABEM) and American Board of Internal Medicine (ABIM)‐accredited EM‐IM residencies from 1998 to 2008 were contacted and asked to complete a survey concerning demographics, board certification, fellowships completed, practice setting, academic affiliation, and perceptions about EM‐IM training and careers.

Results:  There were 127 respondents of a possible 163 total graduates for a response rate of 78%. Seventy graduates (55%) practice EM only, 47 graduates (37%) practice both EM and IM, and nine graduates (7%) practice IM or an IM subspecialty only. Thirty‐one graduates (24%) pursued formal fellowship training in either EM or IM. Graduates spend the majority of their time practicing clinical EM in an urban (72%) and academic (60%) environment. Eighty‐seven graduates (69%) spend at least 10% of their time in an academic setting. Most graduates (64%) believe it practical to practice both EM and IM. A total of 112 graduates (88%) would complete EM‐IM training again.

Conclusions:  Dual training in EM‐IM affords a great deal of career opportunities, particularly in academics and clinical practice, in a number of environments. Graduates hold their training in high esteem and would do it again if given the opportunity.
The Association Between Emergency Medical Technician‐Basic (EMT‐B) Exam Score, Length of EMT‐B Certification, and Success on the National Paramedic Certification Exam
Authors: Fernandez Antonio R. , Studnek Jonathan R. , Cone David C.
Published: August 2009

Objectives:  Factors that affect success on the national paramedic certification examination have been identified. However, there are no known studies that have examined success on the paramedic exam with respect to either Emergency Medical Technician‐Basic (EMT‐B) examination score or length of EMT‐B certification (which may reflect field experience gained prior to enrolling in paramedic training). The objectives of this study included assessing the relationship of EMT‐B examination score and length of EMT‐B certification to success on the national paramedic certification examination.

Methods:  Study data were obtained from the National Registry of EMTs (NREMT). First attempts of the NREMT paramedic certification exam from 2002 to 2006 were included. To assure that EMT‐B certification exam scores were recorded, analysis was limited to individuals in the 14 states that have utilized NREMT for initial certification of both EMT‐Bs and paramedics since January 1, 1997. This also facilitated accurate calculations of the length of EMT‐B certification.

Results:  There were 11,163 individuals meeting inclusion criteria, and a complete case analysis was performed on 9,148, of whom 5,826 (63.7%) passed the national paramedic exam. The mean (±SD) score on the EMT‐B cognitive exam was 75.5 (±6.4%), and the mean (±SD) length of EMT‐B certification prior to paramedic testing was 3.2 (±2.3) years. When placed in a logistic regression model, the EMT‐B exam score variable was categorized in quartiles (≤71%, 72%–75%, 76%–79%, and ≥80%), and the length of EMT‐B certification variable was dichotomized (≤1.6 years vs. >1.6 years). With respect to paramedic exam success, after controlling for known confounders, there was an increase in the odds ratio (OR) across each of the quartiles of EMT‐B exam score. The largest difference was seen when comparing the lowest and highest quartiles (paramedic exam pass rates of 45.6 and 80.8%, respectively; OR = 5.4, 95% confidence interval [CI] = 4.7 to 6.2). Individuals whose length of EMT‐B certification was >1.6 years had increased odds of passing the paramedic examination (OR = 1.2, 95% CI = 1.1 to 1.3). The multivariable logistic regression model demonstrated good fit (p = 0.62).

Conclusions:  Both EMT‐B examination score and ength of EMT‐B certification are associated with success on first attempt at the cognitive portion of the national paramedic certification exam. Educators may wish to consider these two factors when determining paramedic program admission standards and/or consider these variables when determining how to allocate program resources.
Altered Motor Activity of Alternative Splice Variants of the Mammalian Kinesin‐3 Protein KIF1B
Authors: Matsushita Masafumi , Yamamoto Ruri , Mitsui Keiji , Kanazawa Hiroshi
Published: August 2009

Several mammalian kinesin motor proteins exist as multiple isoforms that arise from alternative splicing of a single gene. However, the roles of many motor protein splice variants remain unclear. The kinesin‐3 motor protein KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino‐terminal region of the protein. The insertions are located in the loop region containing the lysine‐rich cluster, also known as the K‐loop, and in the hinge region adjacent to the motor domain. To clarify the functions of these alternative splice variants of KIF1B, we examined the biochemical properties of recombinant KIF1B with and without insertion sequences. In a microtubule‐dependent ATPase assay, KIF1B variants that contained both insertions had higher activity and affinity for microtubules than KIF1B variants that contained no insertions. Mutational analysis of the K‐loop insertion revealed that variants with a longer insertion sequence at this site had higher activity. However, the velocity of movement in motility assays was similar between KIF1B with and without insertion sequences. Our results indicate that splicing isoforms of KIF1B that vary in their insertion sequences have different motor activities.
Neurological symptoms in children with intussusception
Authors: Kleizen KJ , Hunck A , Wijnen MH , Draaisma JMTh
Published: August 2009

Aim:  The classical combination of abdominal pain, vomiting, rectal blood loss and a palpable abdominal mass is only present in a minority of children with intussusception. Neurological signs and symptoms have been described, but are not a well understood phenomenon. We performed a retrospective study to ascertain the frequency and nature of these symptoms and to describe the characteristics of the patients presenting in this atypical way.

Methods:  The records of 58 children presenting with intussusception from 2003 to 2008 were reviewed for abdominal and neurological signs and symptoms, duration of symptoms and effectiveness of treatment.

Results:  In 10 out of 58 patients (17%), one or more neurological symptoms were recorded at presentation, with lethargy being the most frequent, followed by hypotonia and fluctuating consciousness. The patients with neurological abnormalities were significantly younger and presented with a shorter duration of symptoms. Therapy was more invasive, although not statistically significant, in this patient category.

Conclusion:  Intussusception should be considered in the differential diagnosis in young children presenting with lethargy, hypotonia and/or sudden alterations of consciousness even in the absence of the classical symptoms of intussusception.
Prospective effects of weight perception and weight comments on psychological health among Chinese adolescents
Authors: Lo Wing‐Sze , Ho Sai‐Yin , Mak Kwok‐Kei , Wong Yee‐Man , Lai Yuen‐Kwan , Lam Tai‐Hing
Published: August 2009

Aim:  To investigate the prospective effects of weight perception of self and weight comments by others on psychological health problems among Chinese adolescents.

Methods:  In the Hong Kong Student Obesity Surveillance project, 8716 adolescents (41.3% boys) aged 14.2 ± 1.7 years were followed prospectively. Logistic regression yielded odds ratios (ORs) for psychological health problems at 1‐year follow‐up by weight comments received and weight perception at baseline (2006), adjusting for each other sociodemographic factors and body mass index.

Results:  Perceived fatness at baseline predicted subsequent headache and feeling stressful with adjusted ORs (95% confidence intervals) of 1.17 (1.03–1.33) and 1.20 (1.03–1.39), respectively. Perceived thinness at baseline did not predict any subsequent health problems. Receiving incorrect weight comments at baseline also predicted headache, feeling stressful and feeling depressed at follow‐up, with adjusted ORs of 1.19 (1.08–1.31), 1.26 (1.04–1.53) and 1.38 (1.10–1.74) respectively. No gender difference was found in the effects of weight perception and weight comments on psychological outcomes.

Conclusions:  In adolescents, perceived fatness and incorrect weight comments predicted psychological health problems at 1‐year follow‐up. Family members, peers and other social contacts should realize the potential adverse effects of their weight comments, and adolescents should be taught how to correctly assess their weight status.
Conformational stability of neuroglobin helix F – possible effects on the folding pathway within the globin family
Authors: Codutti Luca , Picotti Paola , Marin Oriano , Dewilde Sylvia , Fogolari Federico , Corazza Alessandra , Viglino Paolo , Moens Luc , Esposito Gennaro , Fontana Angelo
Published: August 2009

Neuroglobin is a recently discovered member of the globin family, mainly observed in neurons and retina. Despite the low sequence identity (less than 20% over the whole sequence for the human proteins), the general fold of neuroglobin closely resembles that of myoglobin. The latter is a paradigmatic protein for folding studies, whereas much less is known about the neuroglobin folding pathway. In this work, we show how the structural features of helix F in neuroglobin and myoglobin could represent a pivotal difference in their folding pathways. Former studies widely documented that myoglobin lacks helix F in the apo form. In this study, limited proteolysis experiments on aponeuroglobin showed that helix F does not undergo proteolytic cleavage, suggesting that, also in the apo form, this helix maintains a rigid and structured conformation. To understand better the structural properties of helices F in the two proteins, we analyzed peptides encompassing helix F of neuroglobin and myoglobin in the wild‐type and mutant forms. NMR and CD experiments revealed a helical conformation for neuroglobin helix F peptide, at both pH 7 and pH 2, absent in the myoglobin peptide. In particular, NMR data suggest a secondary structure stabilization effect caused by hydrophobic interactions involving Tyr88, Leu89 and Leu92. Molecular dynamics simulations performed on the apo and holo forms of the two proteins reveal the persistence of helix F in neuroglobin even in the absence of heme. Conversely myoglobin shows a higher mobility of the N‐terminus of helix F on heme removal, which leads to the loss of secondary structure.
A novel, promoter‐based, target‐specific assay identifies 2‐deoxy‐d‐glucose as an inhibitor of globotriaosylceramide biosynthesis
Authors: Okuda Tetsuya , Furukawa Koichi , Nakayama Ken‐ichi
Published: August 2009

Abnormal biosynthesis of globotriaosylceramide (Gb3) is known to be associated with Gb3‐related diseases, such as Fabry disease. The Gb3 synthase gene (Gb3S) codes for α1,4‐galactosyltransferase, which is a key enzyme involved in Gb3 biosynthesis in vivo. Transcriptional repression of Gb3S is a way to control Gb3 biosynthesis and may be a suitable target for the treatment of Gb3‐related diseases. To find a transcriptional inhibitor for Gb3S, we developed a convenient cell‐based chemical screening assay system by constructing a fusion gene construct of the human Gb3S promoter and a secreted luciferase as reporter. Using this assay, we identified 2‐deoxy‐d‐glucose as a potent inhibitor for the Gb3S promoter. In cultured cells, 2‐deoxy‐d‐glucose markedly reduced endogenous Gb3S mRNA levels, resulting in a reduction in cellular Gb3 content and a corresponding accumulation of the precursor lactosylceramide. Moreover, cytokine‐induced expression of Gb3 on the cell surface of endothelial cells, which is closely related to the onset of hemolytic uremic syndrome in O157‐infected patients, was also suppressed by 2‐deoxy‐d‐glucose treatment. These results indicate that 2‐deoxy‐d‐glucose can control Gb3 biosynthesis through the inhibition of Gb3S transcription. Furthermore, we demonstrated the general utility of our novel screening assay for the identification of new inhibitors of glycosphingolipid biosynthesis.
The enzymatic activity of SR protein kinases 1 and 1a is negatively affected by interaction with scaffold attachment factors B1 and 2
Authors: Tsianou Dora , Nikolakaki Eleni , Tzitzira Alexandra , Bonanou Sofia , Giannakouros Thomas , Georgatsou Eleni
Published: August 2009

SR protein kinases (SRPKs) phosphorylate Ser/Arg dipeptide‐containing proteins that play crucial roles in a broad spectrum of basic cellular processes. Phosphorylation by SRPKs constitutes a major way of regulating such cellular mechanisms. In the past, we have shown that SRPK1a interacts with the nuclear matrix protein scaffold attachment factor B1 (SAFB1) via its unique N‐terminal domain, which differentiates it from SRPK1. In this study, we show that SAFB1 inhibits the activity of both SRPK1a and SRPK1 in vitro and that its RE‐rich region is redundant for the observed inhibition. We demonstrate that kinase activity inhibition is caused by direct binding of SAFB1 to SRPK1a and SRPK1, and we also present evidence for the in vitro binding of SAFB2 to the two kinases, albeit with different affinity. Moreover, we show that both SR protein kinases can form complexes with both scaffold attachment factors B in living cells and that this interaction is capable of inhibiting their activity, depending on the tenacity of the complex formed. Finally, we present data demonstrating that SRPK/SAFB complexes are present in the nucleus of HeLa cells and that the enzymatic activity of the nuclear matrix‐localized SRPK1 is repressed. These results suggest a new role for SAFB proteins as regulators of SRPK activity and underline the importance of the assembly of transient intranuclear complexes in cellular regulation.

Structured digital abstract

MINT‐7228149: SRPK1 (uniprotkb:Q96SB4‐2) phosphorylates (MI:0217) Nt‐LBR (uniprotkb:Q14739) by protein kinase assay (MI:0424)

MINT‐7228207: SRPK1 (uniprotkb:Q96SB4‐2) physically interacts (MI:0915) with SAFB1C (uniprotkb:Q15424) by pull down (MI:0096)

MINT‐7228438: SRPK1a (uniprotkb:Q96SB4‐3) physically interacts (MI:0915) with SAFB1C (uniprotkb:Q15424) by pull down (MI:0096)

MINT‐7228306: SRPK1 (uniprotkb:Q14151) physically interacts (MI:0915) with SAFB2C (uniprotkb:Q14151) by pull down (MI:0096)

MINT‐7228452: SRPK1a (uniprotkb:Q96SB4‐3) physically interacts (MI:0915) with SAFB2C (uniprotkb:Q14151) by pull down (MI:0096)

MINT‐7228466: SRPK1 (uniprotkb:Q96SB4‐2) physically interacts (MI:0915) with SAFB1 (uniprotkb:Q15424) by anti tag coimmunoprecipitation (MI:0007)

MINT‐7228500: SRPK1a (uniprotkb:Q96SB4‐3) physically interacts (MI:0915) with SAFB1 (uniprotkb:Q15424) by anti tag coimmunoprecipitation (MI:0007)

MINT‐7228483: SRPK1 (uniprotkb:Q14151) physically interacts (MI:0915) with SAFB2 (uniprotkb:Q14151) by anti tag coimmunoprecipitation (MI:0007)
CAP2 enhances germination of transgenic tobacco seeds at high temperature and promotes heat stress tolerance in yeast
Authors: Shukla Rakesh Kumar , Tripathi Vineeta , Jain Deepti , Yadav Rajiv Kumar , Chattopadhyay Debasis
Published: August 2009

We reported earlier that ectopic expression of CAP2, a single AP2 domain containing transcription activator from chickpea (Cicer arietinum) in tobacco improves growth and development, and tolerance to dehydration and salt stress, of the transgenic plants. Here, we report that, in addition, the CAP2‐transgenic tobacco seeds also exhibit higher germination efficiency at high temperature and show higher expression levels of genes for tobacco heat shock proteins and a heat shock factor. CAP2 was able to activate the 5′‐upstream activating sequence of tobacco heat shock factor. Surprisingly, expression of CAP2 cDNA in Saccharomyces cerevisiae also enhanced heat tolerance, with increased expression of the gene for yeast heat shock factor 1 (Hsf1) and its target, the gene for yeast heat shock protein 104 (Hsp104). Sequence analysis of the Hsf1 promoter revealed the presence of a dehydration‐responsive element/C‐repeat‐like element (DRE/CRE). Recombinant CAP2 protein bound to the DRE/CRE in the Hsf1 promoter in a gel shift assay and transactivated the Hsf1 promoter–His reporter construct. The full‐length CAP2 protein was required to provide thermotolerance in yeast. If these findings are taken together, our results suggest that CAP2 is involved in the heat stress response and provides an example of functioning of a plant transcription factor in yeast, highlighting the strong evolutionary conservation of the stress response mechanism.
Diagnostic Utility of Plasma N‐Terminal Pro‐B‐Type Natriuretic Peptide and C‐Reactive Protein Levels in Differential Diagnosis of Pericardial Constriction and Restrictive Cardiomyopathy
Authors: Karaahmet Tansu , Yilmaz Fatih , Tigen Kursat , Mutlu Bulent , Cevik Cihan , Basaran Yelda
Published: August 2009

The authors investigated the diagnostic utility of plasma N‐terminal pro‐B‐type natriuretic peptide (NT proBNP) and C‐reactive protein (CRP) levels in the differential diagnosis of constrictive pericarditis (CP) and restrictive cardiomyopathy (RC). Twenty‐five patients with high clinical suspicion of either CP or RC were enrolled. Mean plasma NT proBNP levels were significantly higher in patients with RC compared to those with CP (2641 ± 2902 pg/mL vs 628 ± 678 pg/mL; P=.003). The NT proBNP level that provided the best sensitivity and specificity for the differentiation of CP and RC was 800 pg/mL. Mean CRP levels were higher in patients with CP than with RC (1.41 ± 1.73 mg/dL vs 0.38 ± 0.21 mg/dL; P=.03). The CRP level that provided the best sensitivity and specificity for the differentiation of CP and RC was 0.57 mg/dL. Plasma NT proBNP and CRP levels can be useful in the differential diagnosis of RC and CP.
Carbohydrate Antigen 125 Predicts Long‐Term Mortality in African American Patients With Acute Decompensated Heart Failure
Authors: Mansour Ibrahim N. , Napan Sirikarn , Tarek Alahdab M. , Stamos Thomas D.
Published: August 2009

Congest Heart Fail. 2010;16:15–20. ©2009 Wiley Periodicals, Inc.

The goal of this study was to evaluate the relation between serum levels of carbohydrate antigen 125 (CA125) and prognosis in African American (AA) patients with heart failure (HF). Little is known about the usefulness of CA125 in the AA population, which has different pathophysiology and higher prevalence of HF. The authors enrolled 172 consecutive AA patients (mean age, 55.8 years; 61.1% men) admitted with a clinical diagnosis of acute decompensated HF. CA125 was measured within 48±12 hours of presentation. Patients were grouped according to CA125 levels into quartiles. The median CA125 level was 16 U/mL. Serum levels of CA125 were elevated (>35 U/mL) in 58 patients (33.7%). Fifty‐two patients (30.8%) died over a median follow‐up period of 40 months. The CA125 threshold derived from the receiver operating characteristic curves for the prediction of mortality was 35 U/mL. In a multivariate analysis, CA125 levels >35 U/mL were found to be predictive of 40‐month all‐cause mortality (adjusted hazard ratio, 2.53; confidence interval, 1.40–4.59; P=.002). However, CA125 levels were not associated with 18‐month HF rehospitalization. CA125 value is a strong and independent predictor of long‐term mortality in AA patients admitted with a diagnosis of acute decompensated HF. Identifying a higher‐risk cohort might allow for a more targeted treatment approach.
The Determination of Total Hydrogen, Carbon, Nitrogen and Sulfur in Silicates, Silicate Rocks, Soils and Sediments
Authors: Andrade Sandra , Ulbrich Horstpeter H. , Janasi Valdecir A. , Navarro Margareth S.
Published: August 2009

Determinations of the volatile elements carbon, hydrogen, sulfur and nitrogen in many geological RM, performed with the LECO CHN and SC analysers, are presented. The method allowed the determination of S in concentrations from a few % m/m to 0.001% m/m or less, of C from % m/m to 0.01% m/m and of H from % m/m to 0.004% m/m. Accuracy was usually better than the XRF method (for S). All obtained values passed the Sutarno‐Steger test, which establishes that |(meananalysed ‐ meancertified)|/ Scertified < 2, for the cases with an appropriate number of determinations (n > 10 for each element). It was possible to perform routine determination of C, H and S with the instrumentation, coupled with the determination of major and minor elements in geological materials. Determination of nitrogen could also be performed on an exploratory basis, with improvements in the method dependent on the future availability of more reference materials with reliable composition of this element.
Improvements in Digestion Protocols for Trace Element and Isotope Determinations in Stream and Lake Sediment Reference Materials (JSd‐1, JSd‐2, JSd‐3, JLk‐1 and LKSD‐1)
Authors: Révillon Sidonie , Hureau‐Mazaudier Danièle
Published: August 2009

Total dissolution is a critical step in geochemical analysis. Despite the number of published protocols, this issue still draws attention for sediment samples, which are particularly difficult to dissolve due to the common occurrence and high abundance of refractory phases such as zircon. We present tests of different chemical digestion procedures carried out on reference materials (RM) of stream (JSd‐1, JSd‐2 and JSd‐3) and lake (JLk‐1 and LKSD‐1) sediments from the Geological Survey of Japan (GSJ) and the Canadian Certified Reference Material Programme (CCRPM). We demonstrate that the fusion technique is not appropriate for our studies as not all elements of interest were recovered and blank levels were too high to permit further Sr and Pb isotopic composition measurements. Similarly, conventional HF+HNO3 dissolution methods were not efficient enough for detrital samples. Our preferred method involved using high pressure Teflon® vessel bombs in association with HClO4. This protocol ensured a complete dissolution of the powder, as well as a complete recovery of trace elements. Moreover, blank levels were sufficiently low that Sr or Pb isotope compositions could be measured from the same mother solution. We also tested the homogeneity of RM powders by performing tests on various amount of powder.
Structure, optical, and magnetic properties of facing-target reactive sputtered Ti1−xFexO2−δ films
Authors: Jiang Y. B. , Mi W. B. , Jiang E. Y. , Bai H. L.
Published: August 2009

Structure, optical, and magnetic properties of the anatase Ti1−xFexO2−δ films fabricated by facing-target reactive sputtering were investigated. Structural analyses indicate that there are no impurity phases in the films and the grain size reaches maximum when Fe content x is 0.017. The optical band gap of the Ti1−xFexO2−δ films decreases with the increasing x. Photoluminescence (PL) spectra show that direct and indirect band-to-band transitions coexist, and the indirect radiative recombination can be regarded as a one photon and two phonon coupling courses. The PL intensity due to oxygen vacancies enhances and the refractive index of the fims increases with the increasing x. The Ti1−xFexO2−δ films exhibit room-temperature ferromagnetism due to the oxygen vacancies.
Critical evaluation of band bending determination in organic films from photoemission measurements
Authors: Ivanco J. , Zahn D. R. T.
Published: August 2009

Electronic properties of conjugated films, namely, the band bending as derived from photoemission spectroscopy, are critically discussed. The study demonstrates that conclusions on the presence of the band bending deduced from the shift of electronic energy levels with the organic film thickness may be erroneous if the analysis does not consider the evolution of the film’s work function. The work function change—besides that being induced by the interfacial dipole—may occur due to the change in the molecular orientation from the lying down toward upright, as it often occurs with the increased thickness of molecular films.
Improved Parameter Estimation for First‐Order Markov Process
Authors: Batra Deepak , Sharma Sanjay , Kohli Amit Kumar
Published: August 2009

This correspondence presents a linear transformation, which is used to estimate correlation coefficient of first‐order Markov process. It outperforms zero‐forcing (ZF), minimum mean‐squared error (MMSE), and whitened least‐squares (WTLSs) estimators by controlling output noise variance at the cost of increased computational complexity.
Dynamic Tracking of Lung Deformation during Breathing by Using Particle Method
Authors: Chhatkuli Subas , Koshizuka Seiichi , Uesaka Mitsuru
Published: August 2009

To reduce the side effects and to improve the efficiency of radiation therapy in lung cancer, a pinpoint radiation therapy system is under development. In the system, the movement of lung tumor during breathing could be estimated by employing a suitable numerical modeling technique. This paper presents a gridless numerical technique called Moving Particle Semi-implicit (MPS) method to simulate the lung deformation during breathing. The potential of the proposed method to employ in the future pinpoint radiation therapy system has been explored. Deformation of lung during breathing was dynamically tracked and compared against the experimental results at two different locations (upper lobe and lower lobe). Numerical simulations showed that the deformation of lung surface ranged from less than 4 mm to over 20 mm depending on the location at the surface of lung. The simulation showed that the lower section of lung exhibited comparatively large displacement than the upper section. Comparing with the experimental data, the lung surface displacement during inspiration process was predicted reasonably well. Comparison of numerical prediction with experimental observations showed that the root mean squared error was about 2 mm at lower lobe and less than 1 mm at upper lobe at lung surface.
An Early Abdominal Wall Ectopic Pregnancy Successfully Treated with Ultrasound Guided Intralesional Methotrexate: A Case Report
Authors: Anderson Paynesha M. , Opfer Erin K. , Busch Jeanne M. , Magann Everett F.
Published: August 2009

Background. The upper anterior abdominal wall is a very unusual location for an ectopic pregnancy making optimal management uncertain.Case. We report the case of a 26-year-old gravida 4, para 1, aborta 2 with a rising quantitative human chorionic gonadotropin level following a negative diagnostic laparoscopic examination. She was subsequently diagnosed with an abdominal wall ectopic pregnancy 2 cm inferior to the liver. A single percutaneous intralesional injection of methotrexate was successful after initial failure with systemic methotrexate.Conclusion. Systemic methotrexate is a logical first choice for management of a stable early abdominal wall pregnancy. Direct intralesional injection of methotrexate as the next treatment choice may avoid the morbidity linked with operative management.
Bearing and Range Estimation Algorithm for Buried Object in Underwater Acoustics
Authors: Han Dong , Fossati Caroline , Bourennane Salah , Saidi Zineb
Published: August 2009

A new algorithm which associates (Multiple Signal Classification) MUSIC with acoustic scattering
model for bearing and range estimation is proposed. This algorithm takes into account the reflection and the refraction of wave in the interface of water‐sediment in underwater acoustics. A new directional vector, which contains the Direction‐Of‐Arrival
(DOA) of objects and objects‐sensors distances, is used in MUSIC algorithm instead of classical model. The influence of the depth
of buried objects is discussed. Finally, the numerical results are given in the case of buried cylindrical shells.
Myopathy with Concurrent Tadalafil and Simvastatin
Authors: Gargante Maria Pia , Vacante Marco , Russo Cristina , Malaguarnera Mariano
Published: August 2009

A 48-year-old man, using statin, was admitted to hospital with progressive myalgia after consumption of tadalafil and simvastatin. Muscle pain and penile erection disappeared seven days after interruption of therapy. This case demonstrates the interaction of tadalafil with simvastatin resulting in myopathy. Muscle damage could be attributed to the common metabolic way of these two drugs which is cytochrome P450 isoenzyme system.
Valproic Acid-Induced Myoclonus in a Demented Patient: A Case Report
Authors: Gardner Tina M. , Aziz Rehan , Muralee Sunanda , Tampi Rajesh R.
Published: August 2009

Valproic acid and its derivatives are now commonly used to treat various psychiatric disorders in the elderly. Data indicates that the elderly patients are more susceptible to developing neuropsychiatric complications when treated with these medications. In this report, we describe the case of a 66-year-old woman with early-onset, Alzheimer's type dementia, who developed myoclonus when treated with a valproic acid preparation for behavioral disturbances associated with the dementia.