bluuebunny/crossref_metadata_2025 huggingface dataset:
Dangerous Liaisons? Dating and Drinking Diffusion in Adolescent Peer Networks
Authors: Kreager Derek A. , Haynie Dana L.
Published: September 2011

The onset and escalation of alcohol consumption and romantic relationships are hallmarks of adolescence. Yet only recently have these domains jointly been the focus of sociological inquiry. We extend this literature by connecting alcohol use, dating, and peers to understand the diffusion of drinking behavior in school-based friendship networks. Drawing on Granovetter’s classic concept of weak ties, we argue that adolescent romantic partners are likely to be network bridges, or liaisons, connecting daters to new peer contexts that, in turn, promote changes in individual drinking behaviors and allow these behaviors to spread across peer networks. Using longitudinal data of 449 couples from the National Longitudinal Study of Adolescent Health, we estimate Actor–Partner Interdependence Models and identify unique contributions of partners’ drinking, friends’ drinking, and friends-of-partners’ drinking to daters’ own future binge drinking and drinking frequency. Findings support the liaison hypothesis and suggest that friends-of-partners’ drinking have net associations with adolescent drinking patterns. Moreover, the coefficient for friends-of-partners’ drinking is larger than the coefficient for one’s own peers and generally immune to prior selection. Our findings suggest that romantic relationships are important mechanisms for understanding the diffusion of emergent problem behaviors in adolescent peer networks.
Deferential Differentiation
Authors: Kanevsky Lannie
Published: September 2011

Deferential differentiation occurs when the curriculum modification process defers to students’ preferred ways of learning rather than relying on teachers’ judgments. The preferences of 416 students identified as gifted (grades 3-8) for features of differentiated curriculum recommended for gifted students were compared with those of 230 students not identified as gifted. While thinking of their favorite school subject, they responded to the 110 items on the Possibilities for Learning survey. Most and least popular items are reported in nine thematic categories (pace, collaborative learning, choice, curriculum content, evaluation, open-ended activities, expert knowledge, teacher/student relationship, and sharing learning). Self-pacing, choice of topic, and choice of workmates were most popular with students in both groups. Compared with nonidentified students, more of the students identified as gifted wanted to learn about complex, extracurricular topics and authentic, sophisticated knowledge and interconnections among ideas; to work with others some of the time; and to choose the format of the products of their learning. More students identified as gifted also disliked waiting for the rest of the class and asking for help. Overall, the groups’ preferences differed in degree rather than kind, and reflected cognitive abilities frequently cited as distinguishing characteristics of learners with high ability.
Optimization of machining parameters for multi-performance characteristics in drilling hybrid metal matrix composites
Authors: Rajmohan T , Palanikumar K
Published: September 2011

In this study, an approach based on grey relational analysis and the Taguchi method is used to optimize machining parameters with multiple performance characteristics in drilling hybrid Al 356/SiC-mica composites. Experiments were conducted on a vertical machining centre, and Taguchi’s Quality Concept, a L9, 3-level orthogonal array was chosen for the experiments. The drilling parameters, namely spindle speed, feed rate, drill and wt% of SiC, were optimized based on multiple performance characteristics including thrust force, surface roughness, and torque. The grey relational analysis with multiple performance characteristics indicates that the feed rate and the type of drill are the most significant factors which affect performance. Experimental results have shown that drilling process performance can be improved effectively by using this approach.
Ethnicity, Gender Socialization, and Children’s Attitudes Toward Gay Men and Lesbian Women
Authors: Bos Henny M. W. , Picavet Charles , Sandfort Theo G. M.
Published: September 2011

The aim of the present study was to assess whether children’s attitudes toward gay men and lesbian women differ in relation to their ethnic backgrounds and whether ethnic differences are a result of perceived differential gender socialization practices. Data were collected from children in eight Dutch elementary schools by means of a paper-and-pencil questionnaire administered in the classroom. All children (mean age 11.47; N = 229) lived in the Netherlands; 50.2% had non-Western and 49.8% Western ethnic backgrounds. Children with non-Western ethnic backgrounds reported more negative attitudes toward gays and lesbians. These children perceived more parental pressure to behave in accordance with their gender and showed more negative attitudes toward gender-nonconforming behavior by peers. Hierarchical regression analyses revealed that cultural differences in attitudes toward gay men and lesbian women are partly mediated by differentially perceived parental pressure to behave in accordance with their gender.
Culture and Emotion
Authors: Matsumoto David , Hwang Hyi Sung
Published: September 2011

In this article, the authors integrate the seemingly disparate literature on culture and emotion by offering a biocultural model of emotion that offers three premises heretofore not introduced in the literature: (1) emotions need to be distinguished from other affective phenomena, (2) different types of emotions exist, and (3) within any emotion different domains can be studied. Previous controversies have occurred because writers have called all affective states “emotion” without regard to the type or domain of emotion sampled. The authors argue that not all affective states should be called emotion, that emotions that may be biologically innate are different than those that are not, and that different domains of emotion are more relatively influenced by biology or culture. The authors offer researchers a terminology—biological versus cultural emotions, Priming Reactions, Subjective Experience, and Emotional Meanings—provide hypotheses concerning the relative contributions of biology and culture, review the available literature that supports those hypotheses, and argue that the literature can be somewhat neatly integrated into a cohesive whole. The authors contend that the relative contribution of biological and cultural factors to emotion depends on what emotion is being studied and the specific domain of emotion assessed. While the authors acknowledge that their delineations are not the only or the best delineations that can or should be used, they contend that some kind of delineations should be made and can help to synthesize and integrate a large and seemingly disparate, contradictory literature. The authors offer theirs as a first step in this effort.
Clinical Implications of Pathophysiological and Demographic Covariates on the Population Pharmacokinetics of Trastuzumab Emtansine, a HER2‐Targeted Antibody‐Drug Conjugate, in Patients With HER2‐Positive Metastatic Breast Cancer
Authors: Gupta Manish , LoRusso Patricia M. , Wang Bei , Yi Joo‐Hee , Burris Howard A. , Beeram Muralidhar , Modi Shanu , Chu Yu‐Waye , Agresta Samuel , Klencke Barbara , Joshi Amita , Girish Sandhya
Published: September 2011

Trastuzumab emtansine (T‐DM1) is a HER2‐targeted antibody‐drug conjugate in development for treatment of HER2‐positive cancers. T‐DM1 has been tested as a single agent in a phase I and 2 phase II studies of patients with heavily pretreated metastatic breast cancer (MBC), with the maximum tolerated dose established at 3.6 mg/kg intravenously for every‐3‐week dosing. The authors present results from the population pharmacokinetics analysis for T‐DM1. Population pharmacokinetics for T‐DM1 were characterized using a clinical database of 273 patients from the 3 studies. Pharmacokinetics was best described by a linear 2‐compartment model. Population estimates (interindividual variability [IIV]) for pharmacokinetic parameters were clearance, 0.7 L/d (21.0%); central compartment volume (Vc), 3.33 L (13.2%); peripheral compartment volume (Vp), 0.89 L (50.4%); and intercompartmental clearance, 0.78 L/d. Body weight, albumin, tumor burden, and aspartate aminotransferase levels were identified as statistically significant covariates accounting for interindividual variability in T‐DM1 pharmacokinetics, with body weight having a greater effect on IIV of clearance and Vc than other covariates. T‐DM1 exposure was relatively consistent across the weight range following body weight‐based dosing. This analysis suggests no further T‐DM1 dose adjustments are necessary in heavily pretreated patients with MBC.
Ecological development and validation of a music performance rating scale for five instrument families
Authors: Wrigley William J. , Emmerson Stephen B.
Published: September 2011

This study investigated ways to improve the quality of music performance evaluation in an effort to address the accountability imperative in tertiary music education. An enhanced scientific methodology was employed incorporating ecological validity and using recognized qualitative methods involving grounded theory and quantitative methods involving confirmatory factor analyses. By distilling the disciplinary consensus, this approach enabled the specific definition of the constructs and standards used in university student classical music performance examinations, and provided their refinement with the empirical development of standards-based, criterion-specific rating scales for five instrument families. The study found that the examiners in each instrument family used between 15 to 17 constructs and associated descriptors, and at least two general dimensions referring to technical proficiency and another relating to musicality and interpretation. Analyses showed acceptable internal consistency and construct validity for the scales. Findings suggested that, although several construct and general dimension commonalities were found among the items across all scales, the presence of significant instrument-specific differences suggested that the use of generic rating scales may not provide sufficient content validity. Implications for the application of standards in music performance assessment were discussed.
Urine Phenobarbital Drug Screening
Authors: Guillet Ronnie , Kwon Jennifer M. , Chen SiXaio , McDermott Michael P.
Published: September 2011

This study was done to determine if urine phenobarbital measurements provide a reliable indicator of presence of the drug in neonates. Urine was collected from neonates treated with phenobarbital for clinical indications within 4 to 6 hours of clinically indicated collection of serum phenobarbital levels. Urine samples were also collected from control neonates not treated with phenobarbital. One aliquot was assayed fresh, another frozen at -30°C and assayed 1 to 3 months later. Phenobarbital was assayed using the ONLINE TDM Roche/Hitachi automated clinical chemistry analyzer. Serum and urine concentrations were compared as were fresh and frozen urine measurements. Serum phenobarbital ranged from 5.6 to 52.7 μg/mL. Matched urine samples were 56.6 ± 12.5% of the serum level. Frozen samples were 98.3 ± 8.0% of the fresh samples. Urine phenobarbital concentrations, either fresh or frozen, can be used in neonates as a noninvasive estimate of drug levels.
Unexpected Good Motor and Cognitive Function in an Extremely Premature Child With a History of Perinatal Cerebellar Hemispheric Infarction and Multiple Other Risk Factors for Poor Outcome
Authors: Ley Abigail E. , Golomb Meredith R.
Published: September 2011

Cerebellar infarction is a known possible complication of extreme prematurity, and usually results in severe disability. This report presents a 20-month-old girl (16 months corrected), who was born in a toilet at 24 weeks gestational age. She had multiple neonatal predictors of poor outcome, including unilateral cerebellar hemispheric infarction, grade 3 intraventricular hemorrhage, periventricular leukomalacia, fungal sepsis, patent ductus arteriosus, pulmonary valve stenosis, lack of prenatal care, and poor social situation. Despite all these poor prognostic factors, she was close to meeting corrected-age-appropriate motor and cognitive milestones. The etiology and outcomes of cerebellar infarction in extremely premature neonates, and possible contributors to this child’s function, are discussed.
Thermal design of the vertical machining centre headstock by the forced cooling method
Authors: Jiang S , Min X
Published: September 2011

The headstock thermal drift is a major source of the machining error for a vertical machining centre. However, the research so far reported has been unable to provide a satisfactory method to eliminate the spindle axis dip angle resulting from the thermal drift. In this article, a thermal design is carried out for the vertical machining centre headstock by introducing a dual cooling system, utilizing forced water cooling subsystem and a forced air cooling one. An integrated thermal model of the vertical machining centre headstock has been established by aid of the finite element method, and the appropriate structural parameters of the dual cooling system have been analysed. The theoretical results were verified by an experiment in which the perpendicularity between worktable surface and the spindle axis resulting from the thermal displacement is measured. The results indicate that the thermal behaviour of the vertical machining centre headstock can be improved using the dual cooling method.
Feedback control of laminar flow behind backward-facing step by POD analysis and using perturbed Navier–Stokes equations
Authors: Zare A , Emdad H , Goshtasbirad E
Published: September 2011

The purpose of this article is to design a reduced order model based on the proper orthogonal decomposition/Galerkin projection and perturbation method to develop a non-autonomous model. The resulting model can be used in optimal control of flow over backward-facing step. The main disadvantage of the proper orthogonal decomposition approach for control purposes is that, controlling parameters or inputs do not show up explicitly in the resulting reduced order system. The perturbation method can solve this problem and insert control inputs in the resulting system. The resulting system captures the time-varying influence of the controlling parameters and precisely predicts the Navier–Stokes response to external excitations. At last, optimal control theory is introduced to design a control law for a non-linear forced reduced model, which attempts to minimize the vorticity content in the fluid domain. The test bed is laminar flow behind backward-facing step [Formula: see text] actuated by a pair of blowing/suction jets. Results show that the wall jet can significantly influence the flow field and delay separation, while the perturbation method can predict the flow field in an accurate manner. The method is also found to be fast and efficient in computational time.
Asymmetric thermo-elastic analysis of long cylindrical shells of functionally graded materials by differential quadrature method
Authors: Akbari Alashti R , Khorsand M , Tarahhomi M H
Published: September 2011

Asymmetric thermo-elastic analysis of a long cylindrical shell made of functionally graded material under the effect of thermo-mechanical loadings is carried out. Material properties of the cylindrical shell are assumed to be graded in the radial direction according to a power law function, while the Poisson's ratio is assumed to be constant. Numerical solutions of displacement, stress, and temperature fields are obtained using the Fourier and polynomial differential quadrature methods. The results are compared with the reported analytical solutions which are found to be in very good agreement. The cylindrical shell is considered to be under the effect of both axisymmetric and asymmetric loading conditions. Effects of grading parameter, temperature difference, and the ratio of the outer to inner radii of the cylindrical shell on stresses, displacement, and temperature fields are presented.
Efficacy of different washing solutions and contact times on the microbial quality and safety of fresh-cut paprika
Authors: Das B. Kumar , Kim Ji Gang , Choi Ji Weon
Published: September 2011

The role of different washing solutions and contact times was investigated to determine their use as potential sanitizers for maintaining the microbial quality and food safety of fresh-cut paprika. Samples were cut into small pieces, washed for both 90 and 180 s by different washing solutions: tap water, chlorinated water (100 mg/L and pH 6.5–7), electrolyzed water (pH 7.2) and ozonized water (4 mg/L). Then, samples were packaged in 50 µm polypropylene bags and stored at 5 °C for 12 days, followed by an evaluation of the antimicrobial efficacy of the treatments. Various quality and safety parameters, such as gas composition, color, off-odor, electrical conductivity and microbial numbers, were evaluated during storage. Results revealed insignificant differences in gas composition, and no off-odor was observed in any of the samples during the storage period. However, longer contact time resulted in slightly lower hue angle value than a short one for all washing solutions. Moreover, samples washed with ozone washings showed lower electrolyte leakage than other washing solutions. Samples washed for longer contact time except those washed in ozonized water showed increased microbial numbers during storage. Hence, it has been concluded that longer contact time with ozone has positive effects, whereas the other washing solutions adversely affect the microbial quality and safety aspects of fresh-cut paprika.
Neutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial
Authors: Goodin Douglas S , Hartung Hans-Peter , O’Connor Paul , Filippi Massimo , Arnason Barry , Comi Giancarlo , Cook Stuart , Jeffery Douglas , Kappos Ludwig , Bogumil Timon , Knappertz Volker , Sandbrink Rupert , Beckmann Karola , White Rick , Petkau John , Pohl Christoph
Published: September 2011

Background: The frequency and impact of neutralizing antibodies (NAbs) to interferon beta-1b (IFNβ-1b) on clinical and radiographic outcomes is controversial.

Objective: To assess NAb impact in the BEYOND study.

Methods: 2244 patients were randomized (2:2:1) to receive IFNβ-1b, either 250 or 500 µg, or glatiramer acetate, 20 mg, and observed for 2–3.5 years. NAb titers were determined every 6 months. A titer ≥20 NU/ml was considered NAb positive. Efficacy was compared between NAb-positive and NAb-negative patients, using comprehensive statistical analyses, taking into account the delayed appearance of NAbs, the time-dependent changes in the relapse rate, spontaneous reversions to NAb-negative status, NAb-titer level, and also adjusting for baseline factors.

Results: In the IFNβ-1b 250 µg group, NAb-positive titers were detected (≥ once) in 319 patients (37.0%); of these, 112 (35.1%) reverted to NAb-negative status. In the IFNβ-1b 500 µg group, 340 patients (40.7%) became NAb-positive and 119 (35.0%) reverted to NAb-negative status. In both IFNβ groups, especially the 250 µg arm, NAb-positive status was not associated with a convincing impact on any clinical outcome measure by any statistical analysis. By contrast, in both IFNβ groups, NAbs were associated with a very consistent deleterious impact on most MRI outcomes.

Conclusion: There was a notable dissociation between the impact of NAbs on MRI and clinical outcomes. On MRI measures, the impact was consistent and convincing, whereas on clinical measures a negative impact of NAbs was not found. The basis for this clinico-radiographic paradox is unknown but it suggests that the relationship between NAbs and the therapeutic effects of IFNβ-1b is complex.
Temporal trends of disability progression in multiple sclerosis: findings from British Columbia, Canada (1975–2009)
Authors: Shirani Afsaneh , Zhao Yinshan , Kingwell Elaine , Rieckmann Peter , Tremlett Helen
Published: September 2011

Background: Recent natural history studies suggest that multiple sclerosis (MS) is a more slowly progressing disease than previously thought. These observations are from studies separated by time, geography and methodological approach.

Objectives: We investigated whether MS disease progression has changed over time in British Columbia, Canada.

Methods: The British Columbia MS database was queried for relapsing-onset MS patients with symptom onset from 1975 to <1995, first assessed within 15 years from onset and with at least two Expanded Disability Status Scale (EDSS) scores. Latest follow-up was to 2009. Patients were grouped by 5-year onset intervals (1975 to <1980, 1980 to <1985, 1985 to <1990, 1990 to <1995). Outcome was defined as time to reach sustained and confirmed EDSS 6 within 15 years of disease duration. Kaplan–Meier analysis was used to compare: the proportion of patients reaching EDSS 6 (primary analysis) and the time to EDSS 6 (secondary analysis) across the time-period groups.

Results: A total of 2236 relapsing-onset MS patients (73.4% female; mean age at onset: 32.3 ± 8.8 years) were included. No significant temporal trend was found in the proportion of patients reaching EDSS 6 within 15 years from onset (28.5%, 26.4%, 27.7%, 22.3% for intervals 1975 to <1980, 1980 to <1985, 1985 to <1990, 1990 to <1995, respectively; p = 0.09) or in survival curves for time to reach the outcome ( p = 0.14).

Conclusions: Rates of disease progression remained relatively stable over two decades of MS onset in British Columbia, Canada. Our results suggest that differences in disease progression findings between natural history studies may be related to factors other than time period.
An overview of cancer/testis antigens expression in classical Hodgkin's lymphoma (cHL) identifies MAGE-A family and MAGE-C1 as the most frequently expressed antigens in a set of Brazilian cHL patients
Authors: Inaoka Riguel J , Jungbluth Achim A , Baiocchi Otávio CG , Assis Mariane CG , Hanson Nicole C , Frosina Denise , Tassello Jodie , Bortoluzzo Adriana B , Alves Antonio C , Colleoni Gisele WB
Published: September 2011

Background

Cancer/testis antigens are considered potential targets for immunotherapy due to their tumor-associated expression pattern. Although recent studies have demonstrated high expression of CT45 in classical Hodgkin's lymphomas (cHL), less is known about the expression pattern of other families of CTAs in cHL. We aim to evaluate the expression of MAGE-A family, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO1 and GAGE family in cHL and to correlate their expression with clinical and prognostic factors in cHL.

Methods

Tissue microarray was generated from 38 cHL archival cases from Pathology Department of Universidade Federal de Sao Paulo. Immunohistochemistry (IHC) was done using the following panel of antibodies: MAGE-A family (MA454, M3H67, 57B and 6C1), GAGE (#26), NY-ESO-1 (E978), MAGE-C1/CT7 (CT7-33) and MAGE-C2/CT10 (CT10#5).

Results

We found CTA expression in 21.1% of our cHL series. Among the tested CTAs, only MAGE-A family 7/38 (18.4%) and MAGE-C1/CT7 5/38 (13.2%) were positive in our cHL samples. We found higher CTA positivity in advanced stage (28.6%) compared to early stage (11.8%) disease, but this difference was not statistically significant. Analysis of other clinicopathological subgroups of cHL including histological subtypes, EBV status and response to treatment also did not demonstrate statistical significant differences in CTA expression.

Conclusion

We found CTA expression in 21.1% of cHL samples using our panel. Our preliminary findings suggest that from all CTAs included in this study, MAGE-A family and MAGE-C1/CT7 are the most interesting ones to be explored in further studies.
Implementing knowledge into practice for improved neonatal survival; a cluster-randomised, community-based trial in Quang Ninh province, Vietnam
Authors: Wallin Lars , Målqvist Mats , Nga Nguyen T , Eriksson Leif , Persson Lars-Åke , Hoa Dinh P , Huy Tran Q , Duc Duong M , Ewald Uwe
Published: September 2011

Background

Globally, almost 4 million newborns die during the first 4 weeks of life every year. By increased use of evidence-based knowledge in the healthcare system a large proportion of these neonatal deaths could be prevented. But there is a severe lack of knowledge on effective methods for successful implementation of evidence into practice, particularly in low- and middle-income countries. Recent studies have demonstrated promising results with increased survival among both mothers and newborns using community-based approaches. In Vietnam evidence-based guidelines on reproductive health were launched in 2003 and revised in 2009. The overall objective of the current project is to evaluate if a facilitation intervention on the community level, with a problem-solving approach involving local representatives if the healthcare system and the community, results in improvements of neonatal health and survival.

Methods/Design

The study, which has been given the acronym NeoKIP (Neonatal Health - Knowledge Into Practice), took place in 8 districts composed by 90 communes in a province in northern Vietnam, where neonatal mortality rate was 24/1000 in 2005. A cluster randomised design was used, allocating clusters, as defined as a commune and its correponding Commune Health Center (CHC) to either intervention or control arm. The facilitation intervention targeted staff at healthcare centres and key persons in the communes. The facilitator role was performed by lay women (Women's Union representatives) using quality improvement techniques to initiate and sustain improvement processes targeting identified problem areas. The intervention has been running over 3 years and data were collected on the facilitation process, healthcare staff knowledge in neonatal care and their behaviour in clinical practice, and reproductive and perinatal health indicators. Primary outcome is neonatal mortality.

Discussion

The intervention is participatory and dynamic, focused on developing a learning process and a problem-solving cycle. The study recognises the vital role of the local community as actors in improving their own and their newborns' health, and applies a bottom-up approach where change will be accomplished by an increasing awareness at and demand from grass root level. By utilising the existing healthcare structure this intervention may, if proven successful, be well suited for scaling up.

Trial registration

Current Controlled Trials ISRCTN44599712
Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination
Authors: Jiang Cheng-Gang , Lv Ling , Liu Fu-Rong , Wang Zhen-Ning , Liu Fu-Nan , Li Yan-Shu , Wang Chun-Yu , Zhang Hong-Yan , Sun Zhe , Xu Hui-Mian
Published: September 2011

Background

Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown.

Results

In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P < 0.05). Patients with positive CTGF expression had significantly lower cumulative postoperative 5 year survival rate than those with negative CTGF expression (22.9% versus 48.1%, P < 0.001). We demonstrated that knockdown of CTGF expression significantly inhibited cell growth of gastric cancer cells and decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines.

Conclusions

These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.
An implicit iterative algorithm with errors for two families of generalized asymptotically nonexpansive mappings
Authors: Agarwal Ravi P , Qin Xiaolong , Kang Shin Min
Published: September 2011

In this paper, an implicit iterative algorithm with errors is considered for two families of generalized asymptotically nonexpansive mappings. Strong and weak convergence theorems of common fixed points are established based on the implicit iterative algorithm.

Mathematics Subject Classification (2000) 47H09 · 47H10 · 47J25
The use of LiDCO based fluid management in patients undergoing hip fracture surgery under spinal anaesthesia: Neck of femur optimisation therapy - targeted stroke volume (NOTTS): study protocol for a randomized controlled trial
Authors: Wiles Matthew D , Whiteley William JD , Moran Chris G , Moppett Iain K
Published: September 2011

Background

Approximately 70,000 patients/year undergo surgery for repair of a fractured hip in the United Kingdom. This is associated with 30-day mortality of 9% and survivors have a considerable length of acute hospital stay postoperatively (median 26 days). Use of oesophageal Doppler monitoring to guide intra-operative fluid administration in hip fracture repair has previously been associated with a reduction in hospital stay of 4-5 days. Most hip fracture surgery is now performed under spinal anaesthesia. Oesophageal Doppler monitoring may be unreliable in the presence of spinal anaesthesia and most patients would not tolerate the probes. An alternative method of guiding fluid administration (minimally-invasive arterial pulse contour analysis) has been shown to reduce length of stay in high-risk surgical patients but has never been studied in hip fracture surgery.

Methods

Single-centre randomised controlled parallel group trial. Randomisation by website using computer generated concealed tables. Setting: University hospital in UK. Participants: 128 patients with acute primary hip fracture listed for operative repair under spinal anaesthesia and aged > 65 years. Intervention: Stroke volume guided intra-operative fluid management. Continuous measurement of SV recorded by a calibrated cardiac output monitor (LiDCOplus). Maintenance fluid and 250 ml colloid boluses given to achieve sustained 10% increases in stroke volume. Control group: fluid administration at the responsible (blinded) anaesthetist's discretion. The intervention terminates at the end of the surgical procedure and post-operative fluid management is at the responsible anaesthetist's discretion. Primary outcome: length of acute hospital stay is determined by a blinded team of clinicians. Secondary outcomes include number of complications and total cost of care.

Funding NIHR/RfPB: PB-PG-0407-13073.

Trial registration number

Trial registration: Current Controlled TrialsISRCTN88284896.
How funding structures for HIV/AIDS research shape outputs and utilization: a Swiss case study
Authors: Frey Kathrin , Kübler Daniel
Published: September 2011

Background

Research policy in the field of HIV has changed substantially in recent decades in Switzerland. Until 2004, social science research on HIV/AIDS was funded by specialized funding agencies. After 2004, funding of such research was “normalized” and integrated into the Swiss National Science Foundation as the main funding agency for scientific research in Switzerland. This paper offers a longitudinal analysis of the relationship between the changing nature of funding structures on the one hand and the production and communication of policy‐relevant scientific knowledge in the field of HIV on the other hand.

Methods

The analysis relies on an inventory of all social sciences research projects on HIV in Switzerland that were funded between 1987 and 2010, including topics covered and disciplines involved, as well as financial data. In addition, in‐depth interviews were conducted with 18 stakeholders.

Results

The analysis highlights that the pre‐2004 funding policy ensured good coverage of important social science research themes. Specific incentives and explicit promotion of social science research related to HIV gave rise to a multidisciplinary, integrative and health‐oriented approach. The abolition of a specific funding policy in 2004 was paralleled by a drastic reduction in the number of social science research projects submitted for funding, and a decline of public money dedicated to such research. Although the public administration in charge of HIV policy still acknowledges the relevance of findings from social sciences for the development of prevention, treatment and care, HIV‐related social science research does not flourish under current funding conditions.

Conclusions

The Swiss experience sheds light on the difficulties of sustaining social science research and multidisciplinary approaches related to HIV without specialized funding agencies. Future funding policy might not necessarily require specialized agencies, but should better take into account research dynamics and motivations in the field of social sciences.
Silver triflate catalyzed synthesis of 3-aminoalkylated indoles and evaluation of their antibacterial activities
Authors: Rao Vagicherla Kameshwara , Rao Madharam Sudershan , Jain Navin , Panwar Jitendra , Kumar Anil
Published: September 2011

An efficient, one-pot synthesis was developed for 3-aminoalkylated indoles by three-component coupling reaction of aldehydes, N-methylanilines, and indoles using AgOTf as a catalyst. A series of twenty 3-aminoalkylated indoles was evaluated for their antibacterial activities against both Gram negative and Gram positive bacteria. Compounds 4b and 4r showed good antibacterial activity against both Gram positive and Gram negative strains. However, inversing the property of substituent (from 4r to 4q) resulted in the significant fall in the magnitude of antibacterial activity against Escherichia coli.
First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum
Authors: Yu Willie , Chan-On Waraporn , Teo Melissa , Ong Choon Kiat , Cutcutache Ioana , Allen George E , Wong Bernice , Myint Swe Swe , Lim Kiat Hon , Voorhoeve P Mathijs , Rozen Steve , Soo Khee Chee , Tan Patrick , Teh Bin Tean
Published: September 2011

Background

Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP.

Results

WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector.

Conclusions

The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1.
Loss of Foxd3 Results in Decreased β-Cell Proliferation and Glucose Intolerance During Pregnancy
Authors: Plank Jennifer L. , Frist Audrey Y. , LeGrone Alison W. , Magnuson Mark A. , Labosky Patricia A.
Published: September 2011

A complete molecular understanding of β-cell mass expansion will be useful for the improvement of therapies to treat diabetic patients. During normal periods of metabolic challenges, such as pregnancy, β-cells proliferate, or self-renew, to meet the new physiological demands. The transcription factor Forkhead box D3 (Foxd3) is required for maintenance and self-renewal of several diverse progenitor cell lineages, and Foxd3 is expressed in the pancreatic primordium beginning at 10.5 d postcoitum, becoming localized predominantly to β-cells after birth. Here, we show that mice carrying a pancreas-specific deletion of Foxd3 have impaired glucose tolerance, decreased β-cell mass, decreased β-cell proliferation, and decreased β-cell size during pregnancy. In addition, several genes known to regulate proliferation, Foxm1, Skp2, Ezh2, Akt2, and Cdkn1a, are misregulated in islets isolated from these Foxd3 mutant mice. Together, these data place Foxd3 upstream of several pathways critical for β-cell mass expansion in vivo.
Multistage Triaxial Testing to Estimate Effective Stress Relationships for Unsaturated Compacted Soils
Authors: Khosravi Ali , Alsherif Nahed , Lynch Christopher , McCartney John
Published: September 2011

This paper presents an experimental methodology for using multistage, drained triaxial tests on compacted soils under unsaturated conditions to estimate soil-specific relationships between mean effective stress and matric suction. Tests were performed by applying a matric suction to a soil specimen in a triaxial cell using the axis translation technique with back-pressure, then shearing the specimen under drained conditions until reaching stress-path tangency. The specimen was then unloaded, a new suction was applied, and the shearing process was repeated. The points of maximum principal stress difference for the unsaturated specimen were plotted versus mean effective stress, defined using the degree of saturation as the effective stress parameter, and they were found to correspond well with the critical state line defined from triaxial tests on saturated specimens. The suction stress for the compacted soil tested in this study was observed to increase nonlinearly with suction, tending toward a constant value with increasing suction. Although there are potential changes in soil structure in the specimen during loading, unloading, and reloading, the results indicate that the multistage testing method may be useful for estimating soil-specific effective stress parameters for compacted soils in unsaturated conditions. Furthermore, the fact that differences in the soil-water retention curve of soil specimens subjected to different net confining pressures were observed for the soil tested in this study emphasizes the importance of using soil-specific tests to validate predictive relationships between suction stress and matric suction.
A Nine Amino Acid Domain Is Essential for Mutant Prion Protein Toxicity
Authors: Westergard Laura , Turnbaugh Jessie A. , Harris David A.
Published: September 2011

Transgenic mice expressing prion protein (PrP) molecules with several different internal deletions display spontaneous neurodegenerative phenotypes that can be dose-dependently suppressed by coexpression of wild-type PrP. Each of these deletions, including the largest one (Δ32–134), retains 9 aa immediately following the signal peptide cleavage site (residues 23–31; KKRPKPGGW). These residues have been implicated in several biological functions of PrP, including endocytic trafficking and binding of glycosaminoglycans. We report here on our experiments to test the role of this domain in the toxicity of deleted forms of PrP. We find that transgenic mice expressing Δ23–134 PrP display no clinical symptoms or neuropathology, in contrast to mice expressing Δ32–134 PrP, suggesting that residues 23–31 are essential for the toxic phenotype. Using a newly developed cell culture assay, we narrow the essential region to amino acids 23–26, and we show that mutant PrP toxicity is not related to the role of the N-terminal residues in endocytosis or binding to endogenous glycosaminoglycans. However, we find that mutant PrP toxicity is potently inhibited by application of exogenous glycosaminoglycans, suggesting that the latter molecules block an essential interaction between the N terminus of PrP and a membrane-associated target site. Our results demonstrate that a short segment containing positively charged amino acids at the N terminus of PrP plays an essential role in mediating PrP-related neurotoxicity. This finding identifies a protein domain that may serve as a drug target for amelioration of prion neurotoxicity.
Dynamics of Homology Searching During Gene Conversion inSaccharomyces cerevisiaeRevealed by Donor Competition
Authors: Coïc Eric , Martin Joshua , Ryu Taehyun , Tay Sue Yen , Kondev Jané , Haber James E
Published: September 2011

One of the least understood aspects of homologous recombination is the process by which the ends of a double-strand break (DSB) search the entire genome for homologous templates that can be used to repair the break. We took advantage of the natural competition between the alternative donors HML and HMR employed during HO endonuclease-induced switching of the budding yeast MAT locus. The strong mating-type-dependent bias in the choice of the donors is enforced by the recombination enhancer (RE), which lies 17 kb proximal to HML. We investigated factors that improve the use of the disfavored donor. We show that the normal heterochromatic state of the donors does not impair donor usage, as donor choice is not affected by removing this epigenetic silencing. In contrast, increasing the length of homology shared by the disfavored donor increases its use. This result shows that donor choice is not irrevocable and implies that there are several encounters between the DSB ends and even the favored donor before recombination is accomplished. The increase by adding more homology is not linear; these results can be explained by a thermodynamic model that determines the energy cost of using one donor over the other. An important inference from this analysis is that when HML is favored as the donor, RE causes a reduction in its effective genomic distance from MAT from 200 kb to ∼20 kb, which we hypothesize occurs after the DSB is created, by epigenetic chromatin modifications around MAT.
Differentiation of Carbon Dioxide-Sensing Neurons in Caenorhabditis elegans Requires the ETS-5 Transcription Factor
Authors: Guillermin Manon L , Castelletto Michelle L , Hallem Elissa A
Published: September 2011

Many animals sense environmental gases such as carbon dioxide and oxygen using specialized populations of gas-sensing neurons. The proper development and function of these neurons is critical for survival, as the inability to respond to changes in ambient carbon dioxide and oxygen levels can result in reduced neural activity and ultimately death. Despite the importance of gas-sensing neurons for survival, little is known about the developmental programs that underlie their formation. Here we identify the ETS-family transcription factor ETS-5 as critical for the normal differentiation of the carbon dioxide-sensing BAG neurons in Caenorhabditis elegans. Whereas wild-type animals show acute behavioral avoidance of carbon dioxide, ets-5 mutant animals do not respond to carbon dioxide. The ets-5 gene is expressed in BAG neurons and is required for the normal expression of the BAG neuron gene battery. ets-5 may also autoregulate its expression in BAG neurons. ets-5 is not required for BAG neuron formation, indicating that it is specifically involved in BAG neuron differentiation and the maintenance of BAG neuron cell fate. Our results demonstrate a novel role for ETS genes in the development and function of gas-detecting sensory neurons.
On the minimum size of a point set containing a 5-hole and a disjoint 4-hole
Authors: Bhattacharya Bhaswar , Das Sandip
Published: September 2011

Let H(k; l), k ≦ l denote the smallest integer such that any set of H(k; l) points in the plane, no three on a line, contains an empty convex k-gon and an empty convex l-gon, which are disjoint, that is, their convex hulls do not intersect. Hosono and Urabe [JCDCG, LNCS 3742, 117–122, 2004] proved that 12 ≦ H(4, 5) ≦ 14. Very recently, using a Ramseytype result for disjoint empty convex polygons proved by Aichholzer et al. [Graphs and Combinatorics, Vol. 23, 481–507, 2007], Hosono and Urabe [Kyoto CGGT, LNCS 4535, 90–100, 2008] improve the upper bound to 13. In this paper, with the help of the same Ramsey-type result, we prove that H(4; 5) = 12.
The Bambuí Cohort Study of Aging: methodology and health profile of participants at baseline
Authors: Lima-Costa Maria Fernanda , Firmo Josélia O. A. , Uchôa Elizabeth
Published: September 2011

The cohort study was initiated in 1997 to investigate the incidence and predictors of health outcomes in an elderly population with low socio-economic level. The eligible population consisted of all 1,742 residents in Bambuí, Minas Gerais State, Brazil, aged 60 years and over (1,606 participated). During 10 years of follow-up, 641 participants died and 96 were lost, leading to 13,739 person-years of observation. The baseline health profile of participants revealed a double burden of diseases with high prevalence of chronic non-transmissible diseases and widespread Trypanosoma cruzi infection. The most common health condition was hypertension (61.5%), followed by chronic knee or hand symptoms (43.6%), common mental disorders (38.5%), T. cruzi infection (38.1%), and insomnia (36.7%). In general, the baseline prevalence of mental symptoms and cardiovascular diseases or risk factors was comparable to those found in populations in high income countries.
Locating Translation: On the Question of Japanophone Literature
Authors: Workman Travis
Published: September 2011

Adding-Phoneto the name of a National Language Entails an Expansion of Geographic and Historical Perspective. This expansion of perspective in the national-literature departments of the West was initially made possible by decolonization and the collapse of the European empires, when scholars in francophone studies and anglophone studies rethought the relation between language and culture in the postcolonial moment. While the move to-phonestudies brings with it some potential to reinstate the national-literature paradigm in a different form, it can just as easily mean a departure into questions of transnationalism, transcoloniality, translation, and old and new creolizations. To study literature in terms of-phoneis to assume no longer that language and literature follow the tidy dictates of national sovereignty, national identity, and realpolitik, as these were articulated during the age of high imperialism.
Acting the Dreyfus Affair: History and Theater in the French Classroom
Authors: Fette Julie
Published: September 2011

As a professor of French Studies, I had often wished to develop a course in which students could mount a play in French. Its pedagogical value seemed obvious: performing in a foreign language and managing a theatrical production could help students increase their knowledge of French society while improving pronunciation and vocabulary. However, my lack of expertise in the theory and practice of theater stymied me. I had also often longed to teach a course about the Dreyfus affair. The story of a French officer falsely convicted of selling military secrets to the Germans, which tore apart French society for a decade, it contains plenteous teachable issues about France: nationalism, anti-Semitism, the birth of intellectuals, treason and raison d'état, the rise of the modern press and public opinion, the separation of church and state, Third Republic politics, military justice, Franco-German rivalries, and even handwriting analysis. But I doubted that a French department would welcome a whole course just on the Dreyfus affair.