bluuebunny/crossref_metadata_2025 huggingface dataset:
Intimate partner violence and prescription of potentially addictive drugs: prospective cohort study of women in the Oslo Health Study
Authors: Stene Lise Eilin , Dyb Grete , Tverdal Aage , Jacobsen Geir Wenberg , Schei Berit
Published: April 2012

Objectives

To investigate the prescription of potentially addictive drugs, including analgesics and central nervous system depressants, to women who had experienced intimate partner violence (IPV).

Design

Prospective population-based cohort study.

Setting

Information about IPV from the Oslo Health Study 2000/2001 was linked with prescription data from the Norwegian Prescription Database from 1 January 2004 through 31 December 2009.

Participants

The study included 6081 women aged 30–60 years.

Main outcome measures

Prescription rate ratios (RRs) for potentially addictive drugs derived from negative binomial models, adjusted for age, education, paid employment, marital status, chronic musculoskeletal pain, mental distress and sleep problems.

Results

Altogether 819 (13.5%) of 6081 women reported ever experiencing IPV: 454 (7.5%) comprised physical and/or sexual IPV and 365 (6.0%) psychological IPV alone. Prescription rates for potentially addictive drugs were clearly higher among women who had experienced IPV: crude RRs were 3.57 (95% CI 2.89 to 4.40) for physical/sexual IPV and 2.13 (95% CI 1.69 to 2.69) for psychological IPV alone. After full adjustment RRs were 1.83 (1.50 to 2.22) for physical/sexual IPV, and 1.97 (1.59 to 2.45) for psychological IPV alone. Prescription rates were increased both for potentially addictive analgesics and central nervous system depressants. Furthermore, women who reported IPV were more likely to receive potentially addictive drugs from multiple physicians.

Conclusions

Women who had experienced IPV, including psychological violence alone, more often received prescriptions for potentially addictive drugs. Researchers and clinicians should address the possible adverse health and psychosocial impact of such prescription and focus on developing evidence-based healthcare for women who have experienced IPV.
Loss of epithelial membrane protein-2 expression confers an independent prognosticator in nasopharyngeal carcinoma: a cohort study
Authors: Chen Yi-Hsien , Wu Li-Ching , Wu Wen-Ren , Lin Hung-Jung , Lee Sung-Wei , Lin Ching-Yih , Chang Shih-Lun , Chow Nan-Haw , Huang Hsuan-Ying , Li Chien-Feng , Hsu Han-Ping , Shiue Yow-Ling
Published: April 2012

Objective

To evaluate the expression of epithelial membrane protein-2 (EMP2) protein and its clinicopathological associations in patients with nasopharyngeal carcinoma.

Design

Retrospective population-based cohort study.

Setting

This study was based on a biobank in Chi-Mei Medical Center (Tainan, Taiwan) from 1993 to 2002.

Participants

Biopsies of 124 consecutive nasopharyngeal carcinoma patients without initial distant metastasis and treated with consistent guidelines were assessed. Immunoexpressions of EMP2 were analysed and the outcomes were correlated with clinicopathological features and patient survivals.

Primary and secondary outcome measures

Immunoexpressions of EMP2 were analyzed and the outcomes were correlated with clinicopathological features and patient survivals.

Results

Loss of EMP2 expression (49.2%) was correlated with advanced primary tumour (p=0.044), nodal status (p=0.045) and the 7th American Joint Committee on Cancer stage (p=0.027). In multivariate analyses, loss of EMP2 expression emerged as an independent prognosticator for worse disease-specific survival (DSS; p=0.015) and local recurrence-free survival (LRFS; p=0.030), along with the American Joint Committee on Cancer stages III–IV (p=0.034, DSS; p=0.023, LRFS).

Conclusions

Loss of EMP2 expression is common and associated with adverse prognosticators and might confer tumour aggressiveness through hampering its interaction with specific membrane protein(s) and hence the downstream signal transduction pathway(s).
Systematic reviews to evaluate causation: an overview of methods and application
Authors: Khan Khalid S , Ball Elizabeth , Fox Caroline E , Meads Catherine
Published: April 2012

Currently systematic reviews focus on diagnosis or effectiveness of treatment. It is the understanding of disease aetiology that underpins medical education, practice and research. Whether an association meets causal criteria is usually assessed qualitatively. However, this can also be examined through evidence synthesis and systematic reviews to evaluate disease causation and mechanisms are much needed. It is important in such a review to specify the questions to be addressed regarding causal criteria such as strength, consistency, temporality, specificity, biological gradient, plausibility and experimental evidence. The next step is to conduct a thorough literature search to identify the relevant studies and to assess them for their quality, particularly in relation to the risk of bias, ascertainment of exposures and ascertainment of outcomes. Data synthesis can then examine if the observed associations in collated studies are consistent, strong and temporal using techniques such as meta-analysis, testing for heterogeneity and meta-regression. Biological plausibility and coherence with existing theories can also be examined systematically through an assessment of the basic scientific literature. Experimental evidence might also be collated and synthesised to determine if removal of a causal agent alters the outcome. Through these steps a systematic review can help to establish whether an association is causal or not.
Risk of invasive pneumococcal disease in people admitted to hospital with selected immune-mediated diseases: record linkage cohort analyses
Authors: Wotton Clare J , Goldacre Michael J
Published: April 2012

Background

Invasive pneumococcal disease is a serious infection, and it is an important cause of morbidity and mortality in certain groups of ‘at-risk’ people. Those considered ‘at-risk’ in the UK include very young children, people aged 65 years and older and people with certain serious chronic diseases, asplenia or immunosuppression. There is little evidence about whether people with immune-mediated diseases are at increased risk of pneumococcal disease and therefore may benefit from pneumococcal vaccination.

Methods

Retrospective cohort studies, using linked hospital data, from the longstanding Oxford Record Linkage Study (1963–2008) and from recent English national linked Hospital Episode Statistics (1999–2008); analysis of whether people with immune-mediated diseases are more likely than others to be admitted to hospital for pneumococcal disease; calculation of rate ratio for pneumococcal disease in cohorts with immune-mediated disease compared with control cohorts.

Results

There were elevated rate ratios for many of the immune-mediated diseases, for example, Addison's disease in England 3.8 (95% CI 3.4 to 4.2), autoimmune haemolytic anaemia 4.9 (4.4 to 5.3), Crohn's disease 2.2 (2.1 to 2.3), diabetes mellitus 3.7 (3.4 to 4.1), multiple sclerosis 3.7 (3.5 to 3.8), myxoedema 1.60 (1.58 to 1.63), pernicious anaemia 1.74 (1.66 to 1.83), primary biliary cirrhosis 3.3 (2.9 to 3.7), polyarteritis nodosa 5.0 (4.0 to 6.0), rheumatoid arthritis 2.47 (2.41 to 2.52), scleroderma 4.2 (3.8 to 4.7), Sjogren's syndrome 3.2 (2.9 to 3.5) and systemic lupus erythematosus 5.0 (4.6 to 5.4). Findings in the Oxford and all England data sets were similar.

Conclusions

People admitted to hospital with immune-mediated diseases are at higher risk than those with invasive pneumococcal disease. Vaccination should be considered in this group of patients.
Clean cord care practices and neonatal mortality: evidence from rural Uttar Pradesh, India: Table 1
Authors: Agrawal Praween K , Agrawal Sutapa , Mullany Luke C , Darmstadt Gary L , Kumar Vishwajeet , Kiran Usha , Ahuja Ramesh C , Srivastava Vinod K , Santosham Mathuram , Black Robert E , Baqui Abdullah H
Published: April 2012

Background

About a million newborns die each year in India, accounting for about a fourth of total global neonatal deaths. Infections are among the leading causes of neonatal mortality. Care practices immediately following delivery contribute to newborns' risk of infection and mortality.

Objectives

This study examined the association between clean cord care practices and neonatal mortality in rural Uttar Pradesh, India.

Methods

The study used data from a household survey conducted to evaluate a community-based intervention program in two districts of Uttar Pradesh, India. Analysis included data from 5741 singleton live births delivered at home during 2005. The association between clean cord care (clean instrument used to cut cord, clean thread used to tie cord and antiseptics or nothing applied to the cord) and neonatal mortality was estimated using multivariate logistic regression models.

Results

Thirty per cent of the study mothers practiced clean cord care. Neonatal mortality rate was significantly lower among newborns exposed to clean cord care (36.5/1000 live births, 95% CI 28.0 to 46.8) than those who did not practice (53.0/1000 live births, 95% CI 46.1 to 60.6). Clean cord care was associated with 37% lower neonatal mortality (OR=0.63; 95% CI 0.46 to 0.87) after adjusting for mother's age, education, caste/tribe, religion, household wealth, newborn thermal care practice and care-seeking during the first week after birth and study arms.

Conclusions

Promoting clean cord care practice among neonates in community-based maternal and newborn care programs has the potential to improve neonatal survival in rural India and similar other settings.
Towards the next generation of public health research in India: a call for a health equity lens
Authors: Mohindra K S , Mukherjee Subrata , Khan Shamshad , Thresia C U
Published: April 2012

Background

Public health research is at a cross road in India. Despite a high level of health needs and new public health challenges arising in the context of rapid economic growth and social change, public health research is not keeping up with the needs of Indian society. There are, however, new initiatives creating opportunities to increase public health research, thereby raising debates about public health research priorities.

Objective

In this paper, the authors offer their own view on an agenda for the next generation of public health research in India.

Findings

The authors first outline the main reasons why they believe that public health research has been sidelined in India. Then, the authors argue that health equity should be the overarching principle guiding a public health research agenda. The authors suggest how to integrate equity-oriented strategies into the public health research agenda and propose some key research questions that require urgent attention from their respective disciplines.
Mobilising community collectivisation among female sex workers to promote STI service utilisation from the government healthcare system in Andhra Pradesh, India
Authors: Parimi Prabhakar , Mishra Ram Manohar , Tucker Saroj , Saggurti Niranjan
Published: April 2012

Background

To assess the association between female sex workers' (FSWs) degree of community collectivisation and self-efficacy, utilisation of sexually transmitted infection (STI) services from government-run health centres in Andhra Pradesh, India.

Methods

Cross-sectional analyses of 1986 FSWs recruited using a probability-based sampling from five districts of Andhra Pradesh during 2010–2011. Multiple logistic regression models were constructed to assess associations. The independent variables included—collective efficacy, collective agency and collective action—measured using a series of items that assessed the grouping of the community on issues that concern most sex workers. An additional independent variable included FSWs belonging to an area where there was a project partnership with government health centres to provide STI treatment services to FSWs. The outcome indicators included self-efficacy for service utilisation from government health facilities and the treatment for STIs from government health facilities at least once in the past year experience of STI symptoms.

Results

Of the 1986 FSWs, nearly two-fifths (39.5%) reported a high level of overall collectivisation (collective efficacy: 89%, collective agency: 50.7%; collective action: 12.7%). Sex workers with a high degree compared with low degree of overall collectivisation were significantly more likely to report high self-efficacy to use government health facilities (75.0% vs 57.3%, adjusted OR 2.5, 95% CI 2.0 to 3.1) and to use government health centres for STI treatment in past 1 year (78.1% vs 63.2%, adjusted OR 2.1, 95% CI 1.6 to 2.8), irrespective of project partnership with government centres.

Conclusion

The current research findings reinforce the need for stronger community mobilisation for better utilisation of government health facilities for STI and HIV prevention interventions.
Characterization of arsenic species in microbial mats from an inactive gold mine
Authors: Foster Andrea L. , Ashley Roger P.
Published: April 2012

Filamentous cyanobacterial mats and Fe oxyhydroxide-rich bacterial mats collected near an inactive gold mine in California are enriched in arsenic (As) approximately 1000-fold relative to the waters in contact with them. The predominant organism in the cyanobacterial mat could not be identified using morphological characteristics, but the unique morphology of the sheath-forming β protobacterium
Leptothrix ochracea
was used to identify this species in Fe oxyhydroxide mat samples from several sites near the gold mine.
Leptothrix
sheaths commonly exceed 10 μm in length and have an average diameter of 1 μm. The Fe-oxyhydroxide mats are dominated by
L. ochracea
sheaths, but use of fluorescently tagged genetic stains reveals the presence of sheathless bacteria that presumably also promote the formation of Fe oxyhydroxide. X-ray absorption fine structure (XAFS) spectroscopy was used to identify As species in these microbial mats. Mat-associated As is predominantly As(V), even when As(III) is the primary dissolved species in contact with the mats. The species of As(V) associated with the cyanobacterial mat could not be conclusively identified; however, it is not associated with Fe oxyhydroxide or other minerals, based on comparison to XAFS spectra of As adsorbed to various substrates. In addition, the cyanobacterial mat XAFS spectrum is different from that of aqueous As(V), suggesting that As(V) in the mat lacks some or all of the coordinating water molecules present in aqueous solution. We hypothesize that As is associated with the exopolysaccharide (EPS) matrix secreted by the cyanobacteria. In
Leptothrix
-dominated Fe-oxyhydroxide bacterial mats, XAFS analysis clearly indicates that As(V) is associated with the Fe oxyhydroxide as an adsorbed and/or coprecipitated complex.
Middle Pleistocene landforms in the Danish Sector of the southern North Sea imaged on 3D seismic data
Authors: Müther Dagmar , Back Stefan , Reuning Lars , Kukla Peter , Lehmkuhl Frank
Published: April 2012

Despite a long history of investigation, several critical issues regarding the glacial history of NW Europe, particularly in currently marine areas, remain unsolved. In this study, we present a comprehensive three-dimensional (3D) seismic interpretation of an area measuring 2000 km
2
in the western part of the Danish North Sea that exhibits several buried Quaternary landforms. Well data are used to assign minimum and maximum ages for the studied sedimentary succession. The most prominent buried landforms are three large-scale tunnel valleys of probable Saalian age that extend over more than 20 km across the western and southern part of the study area. These valleys most probably formed through subglacial meltwater erosion close to the termination of a former ice sheet. In the southern part of the study area, an extensive network of small-scale, dendritic seismic lineations interpreted as a palaeo-drainage system characterizes the landward termination of one major tunnel valley. This drainage system was active either contemporaneously or shortly after the development of the tunnel valley. Interpretation of this system as contemporaneous to tunnel-valley formation suggests that steady-state subglacial meltwater discharge was funnelled through a drainage system into the main tunnel valley. In contrast, interpretation of the drainage network as post-incisional points to the development of a post-glacial river system re-using the pre-existing tunnel valley as a downstream fluvial pathway. This uncertainty in the interpretation has important consequences for prediction of the rock content and reservoir characteristics of the tunnel-valley infill, in that either meltwater deposits or fluvial sediments form a considerable part of the tunnel-valley infill.
Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury
Authors: Lapchak Peter H. , Kannan Lakshmi , Rani Poonam , Pamuk Omer Nuri , Ioannou Antonis , Dalle Lucca Jurandir J. , Pine Polly , Tsokos George C.
Published: April 2012

Tissue injury following ischemia-reperfusion (I/R) occurs as a consequence of actions of soluble factors and immune cells. Growing evidence supports a role for platelets in the manifestation of tissue damage following I/R. Spleen tyrosine kinase has been well documented to be important in lymphocyte activation and more recently in platelet activation. We performed experiments to evaluate whether inhibition of platelet activation through inhibition of spleen tyrosine kinase prevents tissue damage after mesenteric I/R injury. Platelets isolated from C57BL/6J mice fed with R788 for 10 days were transfused into C57BL/6J mice depleted of platelets 2 days before mesenteric I/R injury. Platelet-depleted mice transfused with platelets from R788-treated mice before mesenteric I/R displayed a significant reduction in the degree of remote lung damage, but with little change in the degree of local intestinal damage compared with control I/R mice. Transfusion of R788-treated platelets also decreased platelet sequestration, C3 deposition, and immunoglobulin deposition in lung, but not in the intestine, compared with control groups. These findings demonstrate that platelet activation is a requisite for sequestration in the pulmonary vasculature to mediate remote tissue injury after mesenteric I/R. The use of small-molecule inhibitors may be valuable to prevent tissue damage in remote organs following I/R injury.
Effects of β2-agonists on force during and following anoxia in rat extensor digitorum longus muscle
Authors: Fredsted A. , Gissel H. , Ørtenblad N. , Clausen T.
Published: April 2012

Electrical stimulation of isolated muscles may lead to membrane depolarization, gain of Na+, loss of K+ and fatigue. These effects can be counteracted with β2-agonists possibly via activation of the Na+-K+ pumps. Anoxia induces loss of force; however, it is not known whether β2-agonists affect force and ion homeostasis in anoxic muscles. In the present study isolated rat extensor digitorum longus (EDL) muscles exposed to anoxia showed a considerable loss of force, which was markedly reduced by the β2-agonists salbutamol (10−6 M) and terbutaline (10−6 M). Intermittent stimulation (15–30 min) clearly increased loss of force during anoxia and reduced force recovery during reoxygenation. The β2-agonists salbutamol (10−7-10−5 M) and salmeterol (10−6 M) improved force development during anoxia (25%) and force recovery during reoxygenation (55–262%). The effects of salbutamol on force recovery were prevented by blocking the Na+-K+ pumps with ouabain or by blocking glycolysis with 2-deoxyglucose. Dibutyryl cAMP (1 mM) or theophylline (1 mM) also improved force recovery remarkably. In anoxic muscles, salbutamol decreased intracellular Na+ and increased 86Rb uptake and K+ content, indicating stimulation of the Na+-K+ pumps. In fatigued muscles salbutamol induced recovery of excitability. Thus β2-agonists reduce the anoxia-induced loss of force, leading to partial force recovery. These data strongly suggest that this effect is mediated by cAMP stimulation of the Na+-K+ pumps and that it is not related to recovery of energy status (PCr, ATP, lactate).
Novel Power Reduction Technique for ReRAM with Automatic Avoidance Circuit for Wasteful Overwrite
Authors: Handa Takaya , Yoshimoto Yuhei , Nakayama Kazuya , Kitagawa Akio
Published: April 2012

Low-power operations can be great advantageous for ReRAM devices. However, wasteful overwriting such as the SET operation to low-resistance state (LRS) device and the RESET operation to high-resistance state (HRS) device causes not only an increase in power but also the degradation of the write cycles due to repeatedly rewriting. Thus, in this paper, we proposed a novel automatic avoidance circuit for dealing with wasteful overwriting that uses a sense amplifier and estimated the energy consumption reduction rate by conducting a circuit simulation. As a result, this circuit helped to reliably avoid the wasteful overwriting operation to reduce about 99% and 97% of wasteful energy using VSRC and CSRC, respectively.
Blood Pressure over Height Ratios: Simple and Accurate Method of Detecting Elevated Blood Pressure in Children
Authors: Galescu Ovidiu , George Minu , Basetty Sudhakar , Predescu Iuliana , Mongia Anil , Ten Svetlana , Bhangoo Amrit
Published: April 2012

Background. Blood pressure (BP) percentiles in childhood are assessed according to age, gender, and height.Objective. To create a simple BP/height ratio for both systolic BP (SBP) and diastolic BP (DBP). To study the relationship between BP/height ratios and corresponding BP percentiles in children.Methods. We analyzed data on height and BP from 2006-2007 NHANES data. BP percentiles were calculated for 3775 children. Receiver-operating characteristic (ROC) curve analyses were performed to calculate sensitivity and specificity of BP/height ratios as diagnostic tests for elevated BP (>90%). Correlation analysis was performed between BP percentiles and BP/height ratios.Results. The average age was 12.54 ± 2.67 years. SBP/height and DBP/height ratios strongly correlated with SBP & DBP percentiles in both boys (, , ) and girls (, , ). The cutoffs of SBP/height and DBP/height ratios in boys were ≥0.75 and ≥0.46, respectively; in girls the ratios were ≥0.75 and ≥0.48, respectively with sensitivity and specificity in range of 83–100%.Conclusion. BP/height ratios are simple with high sensitivity and specificity to detect elevated BP in children. These ratios can be easily used in routine medical care of children.
Active Sliding Mode Control Antisynchronization of Chaotic Systems with Uncertainties and External Disturbances
Authors: Jawaada Wafaa , Noorani M. S. M. , Al-sawalha M. Mossa
Published: April 2012

The antisynchronization behavior of chaotic systems with parametric uncertainties and external disturbances is explored by using robust active sliding mode control method. The sufficient conditions for achieving robust antisynchronization of two identical chaotic systems with different initial conditions and two different chaotic systems with terms of uncertainties and external disturbances are derived based on the Lyapunov stability theory. Analysis and numerical simulations are shown for validation purposes.
Biofuels Production from Biomass by Thermochemical Conversion Technologies
Authors: Verma M. , Godbout S. , Brar S. K. , Solomatnikova O. , Lemay S. P. , Larouche J. P.
Published: April 2012

Agricultural biomass as an energy resource has several environmental and economical advantages and has potential to substantially contribute to present days’ fuel demands. Currently, thermochemical processes for agricultural biomass to energy transformation seem promising and feasible. The relative advantage of thermochemical conversion over others is due to higher productivity and compatibility with existing infrastructure facilities. However, the majority of these processes are still under development phase and trying to secure a market share due to various challenges, right from suitable infrastructure, raw material, technical limitations, government policies, and social acceptance. The knowledge at hand suggests that biomass can become a sustainable and major contributor to the current energy demands, if research and development are encouraged in the field of thermochemical conversion for various agricultural biomass types. This paper intends to explore the physical and chemical characteristics of biofuel substitutes of fossil fuels, potential biomass sources, and process parameters for thermochemical conversion.
Where Does Evidence from New Trials for Schizophrenia Fit with the Existing Evidence: A Case of the Emperor's New Clothes?
Authors: Jayaram Mahesh , Rattehalli Ranganath D. , Adams Clive E.
Published: April 2012

Advent of “atypical” antipsychotics has spawned new trials in the recent years and the number of such trial reports has been increasing exponentially. As clinicians we have been led to believe that “atypicals” are better than “typicals” despite the odd dissenting voice in academic and clinical circles. This has been largely ignored until the publication of two landmark, independent, pragmatic trials, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS), which proved that thoughtfully chosen “typical” antipsychotics were as good as the newer “atypicals.” We pooled “leaving the study early data” from Cochrane Reviews that existed before CATIE and CUtLASS and added data from CATIE and CUtLASS to the pool for a “before and after” comparison. Addition of CATIE and CUtLASS data only led to narrowing of the already existing confidence intervals, merely increasing precision, and decreasing the risk of Type II error. Perhaps surprisingly, CATIE and CUtLASS when pooled with the already existing data showed us that we had chosen to turn a blind eye to findings that already existed. This leads clinicians to question as to whether, in future, we need to feel less guilty about crying out early on that the emperor has no clothes on.
Plastic Optical Fiber Sensing of Alcohol Concentration in Liquors
Authors: Morisawa Masayuki , Muto Shinzo
Published: April 2012

A simple optical fiber sensing system of alcohol concentration in liquors has been studied. In this sensor head, a mixture polymer of novolac resin and polyvinylidenefluoride (PVDF) with a ratio of 9 : 1 was coated as a sensitive cladding layer on the plastic fiber core made of polystyrene-(PS-)coated polycarbonate (PC). Using this sensor head and a green LED light source, it was confirmed that alcohol concentration in several kinds of liquors from beer to whisky can easily be measured with a fast response time less than 1 minute.
Approximate Solutions of Fractional Nonlinear Equations Using Homotopy Perturbation Transformation Method
Authors: Liu Yanqin
Published: April 2012

A homotopy perturbation transformation method (HPTM) which is based on homotopy perturbation method and Laplace transform is first applied to solve the approximate solution of the fractional nonlinear equations. The nonlinear terms can be easily handled by the use of He′s polynomials. Illustrative examples are included to demonstrate the high accuracy and fast convergence of this new algorithm.
Comparison of Gelation Time and Polyalcohol Effect on Hydrogels from Domestic and Wild Silk Fibroins
Authors: Zhao Huijing , Xiong Siyong , Li Mingzhong , Zhang Qiang , Liu Guiyang
Published: April 2012

Silk fibroin (SF) hydrogels were obtained from both domestic (Bombyx mori) and wild (Antheraea pernyi) silkworms from aqueous silk fibroin solutions at room temperature. The gelation time of theAntheraea pernyi(A. pernyi) SF solution was significantly shorter than that of theBombyx mori(B. mori) SF solution. The secondary structures of the two kinds of hydrogels were also compared. In order to further reduce the gelation time, various amounts of polyethylene glycol (PEG) were blended with the silk fibroins ofA. pernyiandB. mori. The gelation time of bothA. pernyiSF andB. moriSF decreased with the increased amount of PEG. After freeze-drying, the hydrogels were characterized through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and Raman spectroscopy. Results showed that the addition of polyalcohol did not change the main secondary structure of the hydrogels. However, the addition of polyalcohol did reduce the gelation time and triggered additional formation ofβ-sheets.
The Memory Metal Minimal Access Cage: A New Concept in Lumbar Interbody Fusion—A Prospective, Noncomparative Study to Evaluate the Safety and Performance
Authors: Kok D. , Donk R. D. , Wapstra F. H. , Veldhuizen A. G.
Published: April 2012

Study Design/Objective. A single-centre, prospective, non-comparative study of 25 patients to evaluate the performance and safety of the Memory Metal Minimal Access Cage (MAC) in Lumbar Interbody Fusion.Summary of Background Data. Interbody fusion cages in general are designed to withstand high axial loads and in the meantime to allow ingrowth of new bone for bony fusion. In many cages the contact area with the endplate is rather large leaving a relatively small contact area for the bone graft with the adjacent host bone. MAC is constructed from the memory metal Nitinol and builds on the concept of sufficient axial support in combination with a large contact area of the graft facilitating bony ingrowth and ease in minimal access implantation due to its high deformability.Methods. Twenty five subjects with a primary diagnosis of disabling back and radicular leg pain from a single level degenerative lumbar disc underwent an interbody fusion using MAC and pedicle screws. Clinical performance was evaluated prospectively over 2 years using the Oswestry Disability Index (ODI), Short Form 36 questionnaire (SF-36) and pain visual analogue scale (VAS) scores. The interbody fusion status was assessed using conventional radiographs and CT scan. Safety of the device was studied by registration of intra- and post-operative adverse effects.Results. Clinical performance improved significantly (P<.0018), CT scan confirmed solid fusion in all 25 patients at two year follow-up. In two patients migration of the cage occurred, which was resolved uneventfully by placing a larger size at the subsequent revision.Conclusions. We conclude that the Memory Metal Minimal Access Cage (MAC) resulted in 100% solid fusions in 2 years and proved to be safe, although two patients required revision surgery in order to achieve solid fusion.
Experimental and Numerical Failure Analysis of Adhesive Composite Joints
Authors: Asgari Mehrabadi Farhad
Published: April 2012

In the first section of this work, a suitable data reduction scheme is developed to measure the adhesive joints strain energy release rate under pure mode-I loading, and in the second section, three types of adhesive hybrid lap-joints, that is, Aluminum-GFRP (Glass Fiber Reinforced Plastic), GFRP-GFRP, and Steel-GFRP were employed in the determination of adhesive hybrid joints strengths and failures that occur at these assemblies under tension loading. To achieve the aims, Double Cantilever Beam (DCB) was used to evaluate the fracture state under the mode-I loading (opening mode) and also hybrid lap-joint was employed to investigate the failure load and strength of bonded joints. The finite-element study was carried out to understand the stress intensity factors in DCB test to account fracture toughness using J-integral method as a useful tool for predicting crack failures. In the case of hybrid lap-joint tests, a numerical modeling was also performed to determine the adhesive stress distribution and stress concentrations in the side of lap-joint. Results are discussed in terms of their relationship with adhesively bonded joints and thus can be used to develop appropriate approaches aimed at using adhesive bonding and extending the lives of adhesively bonded repairs for aerospace structures.
Multiferroic Memories
Authors: Roy Amritendu , Gupta Rajeev , Garg Ashish
Published: April 2012

Multiferroism implies simultaneous presence of more than one ferroic characteristics such as coexistence of ferroelectric and magnetic ordering. This phenomenon has led to the development of various kinds of materials and conceptions of many novel applications such as development of a memory device utilizing the multifunctionality of the multiferroic materials leading to a multistate memory device with electrical writing and nondestructive magnetic reading operations. Though, interdependence of electrical- and magnetic-order parameters makes it difficult to accomplish the above and thus rendering the device to only two switchable states, recent research has shown that such problems can be circumvented by novel device designs such as formation of tunnel junction or by use of exchange bias. In this paper, we review the operational aspects of multiferroic memories as well as the materials used for these applications along with the designs that hold promise for the future memory devices.
Lyn Kinase Mediates Cell Motility and Tumor Growth in EGFRvIII-Expressing Head and Neck Cancer
Authors: Wheeler Sarah E. , Morariu Elena M. , Bednash Joseph S. , Otte Charlton G. , Seethala Raja R. , Chiosea Simion I. , Grandis Jennifer R.
Published: April 2012

Purpose: EGF receptor variant III (EGFRvIII) has been detected in several cancers in which tumors expressing this truncated growth factor receptor show more aggressive behavior. The molecular mechanisms that contribute to EGFRvIII-mediated tumor progression that are amenable to targeted therapy are incompletely understood. The present study aimed to better define the role of Src family kinases (SFKs) in EGFRvIII-mediated cell motility and tumor growth of head and neck squamous cell carcinomas (HNSCC).

Experimental Design: HNSCC models expressing EGFRvIII were treated with dasatinib, a pharmacologic inhibitor of SFKs.

Results: SFK inhibition significantly decreased cell proliferation, migration, and invasion of EGFRvIII-expressing HNSCC cells. Administration of dasatinib to mice bearing EGFRvIII-expressing HNSCC xenografts resulted in a significant reduction of tumor volume compared with controls. Immunoprecipitation with anti-c-Src, Lyn, Fyn, and Yes antibodies followed by immunoblotting for phosphorylation of the SFK activation site (Y416) showed specific activation of Lyn kinase in EGFRvIII-expressing HNSCC cell lines and human HNSCC tumor specimens. Selective inhibition of Lyn using siRNA decreased cell migration and invasion of EGFRvIII-expressing HNSCCs compared with vector control cells.

Conclusions: These findings show that Lyn mediates tumor progression of EGFRvIII-expressing HNSCCs in which strategies to inhibit SFK may represent an effective therapeutic strategy. Clin Cancer Res; 18(10); 2850–60. ©2012 AACR.
Evaluation of Circulating Tumor Cells and Circulating Tumor DNA in Non–Small Cell Lung Cancer: Association with Clinical Endpoints in a Phase II Clinical Trial of Pertuzumab and Erlotinib
Authors: Punnoose Elizabeth A. , Atwal Siminder , Liu Weiqun , Raja Rajiv , Fine Bernard M. , Hughes Brett G.M. , Hicks Rodney J. , Hampton Garret M. , Amler Lukas C. , Pirzkall Andrea , Lackner Mark R.
Published: April 2012

Purpose: Elevated levels or increases in circulating tumor cells (CTC) portend poor prognosis in patients with epithelial cancers. Less is known about CTCs as surrogate endpoints or their use for predictive biomarker evaluation. This study investigated the utility of CTC enumeration and characterization using the CellSearch platform, as well as mutation detection in circulating tumor DNA (ctDNA), in patients with advanced non–small cell lung cancer (NSCLC).

Experimental Design: Forty-one patients were enrolled in a single-arm phase II clinical trial of erlotinib and pertuzumab. Peripheral blood was analyzed for CTC enumeration, EGFR expression in CTCs, and detection of oncogenic mutations in CTCs and ctDNA. Changes in CTC levels were correlated with 2[18F]fluoro-2-deoxy-d-glucose–positron emission tomographic (FDG-PET) and computed tomographic (CT) imaging and survival endpoints.

Results: CTCs were detected (≥1 CTC) at baseline in 78% of patients. Greater sensitivity for mutation detection was observed in ctDNA than in CTCs and detected mutations were strongly concordant with mutation status in matched tumor. Higher baseline CTC counts were associated with response to treatment by Response Evaluation Criteria in Solid Tumors (RECIST, P = 0.009) and decreased CTC counts upon treatment were associated with FDG-PET and RECIST response (P = 0.014 and P = 0.019) and longer progression-free survival (P = 0.050).

Conclusion: These data provide evidence of a correlation between decreases in CTC counts and radiographic response by either FDG-PET or RECIST in patients with advanced NSCLC. These findings require prospective validation but suggest a potential role for using CTC decreases as an early indication of response to therapy and ctDNA for real-time assessment of mutation status from blood. Clin Cancer Res; 18(8); 2391–401. ©2012 AACR.
Effect of Small-Molecule–Binding Affinity on Tumor Uptake In Vivo: A Systematic Study Using a Pretargeted Bispecific Antibody
Authors: Orcutt Kelly Davis , Rhoden John J. , Ruiz-Yi Benjamin , Frangioni John V. , Wittrup K. Dane
Published: April 2012

Small-molecule ligands specific for tumor-associated surface receptors have wide applications in cancer diagnosis and therapy. Achieving high-affinity binding to the desired target is important for improving detection limits and for increasing therapeutic efficacy. However, the affinity required for maximal binding and retention remains unknown. Here, we present a systematic study of the effect of small-molecule affinity on tumor uptake in vivo with affinities spanning a range of three orders of magnitude. A pretargeted bispecific antibody with different binding affinities to different DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based small molecules is used as a receptor proxy. In this particular system targeting carcinoembryonic antigen, a small-molecule–binding affinity of 400 pmol/L was sufficient to achieve maximal tumor targeting, and an improvement in affinity to 10 pmol/L showed no significant improvement in tumor uptake at 24 hours postinjection. We derive a simple mathematical model of tumor targeting using measurable parameters that correlates well with experimental observations. We use relations derived from the model to develop design criteria for the future development of small-molecule agents for targeted cancer therapeutics. Mol Cancer Ther; 11(6); 1365–72. ©2012 AACR.
Overcoming Platinum Resistance through the Use of a Copper-Lowering Agent
Authors: Fu Siqing , Naing Aung , Fu Caroline , Kuo Macus Tien , Kurzrock Razelle
Published: April 2012

Low levels of human copper transporter 1 (hCtr1) mRNA are associated with a shorter progression-free survival after platinum-based therapy. Pretreatment with a copper-lowering agent such as trientine enhanced hCtr1-mediated platinum uptake. Therefore, we conducted a pilot study (NCT01178112) of carboplatin and trientine with the goal of resensitizing patients with advanced cancer to platinum chemotherapy. This case report reviews the outcomes of 5 patients with platinum-resistant high-grade epithelial ovarian cancer enrolled on the study to date. Overall, they tolerated treatment well. Severe adverse events that occurred in 2 patients were myelosuppression, notably anemia requiring transfusion. Dose-limiting toxicity was not observed within the first 28 days (cycle 1). After 2 cycles of therapy, partial remission was achieved in 1 patient (10+ months), stable disease in 3 patients (2, 3.5+, and 5 months, respectively), and 1 patient had progressive disease. These cases provide preliminary clinical evidence that the role of decreasing copper levels in reversing platinum resistance merits additional clinical investigation. Evaluation of this novel strategy is warranted in larger studies to assess the efficacy of this approach for treating platinum-resistant advanced epithelial ovarian cancer in patients with high copper levels. Mol Cancer Ther; 11(6); 1221–5. ©2012 AACR.
Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to the Pleiotropic Effect of Cilostazol
Authors: Omote Yoshio , Deguchi Kentaro , Tian FengFeng , Kawai Hiromi , Kurata Tomoko , Yamashita Toru , Ohta Yasuyuki , Abe Koji
Published: April 2012

Background and Purpose—

Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R).

Methods—

Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1Rβ expression in the hippocampus was assessed by Western blotting.

Results—

The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (
P
<0.05) in the memory-related IGF-1R-positive ratio and IGF-1Rβ expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels.

Conclusions—

The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and spatial cognitive functions. The increase of IGF-1R-positive cells in the hippocampal CA1 region could partly explain the preservation of spatial cognitive function in stroke-prone spontaneously hypertensive rats.
Intracranial Hemorrhage in Atrial Fibrillation Patients During Anticoagulation With Warfarin or Dabigatran
Authors: Hart Robert G. , Diener Hans-Christoph , Yang Sean , Connolly Stuart J. , Wallentin Lars , Reilly Paul A. , Ezekowitz Michael D. , Yusuf Salim
Published: April 2012

Background and Purpose—

Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined.

Methods—

Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2–3) or dabigatran (150 mg or 110 mg, both twice daily).

Results—

During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (
P
<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32;
P
<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients;
P
<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9;
P
<0.001), aspirin use (relative risk, 1.6;
P
=0.01), age (relative risk, 1.1 per year;
P
<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8;
P
=0.001).

Conclusions—

The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.
Spatial Presence and Perceived Reality as Predictors of Motion-Based Video Game Enjoyment
Authors: Shafer Daniel M. , Carbonara Corey P. , Popova Lucy
Published: April 2012

This study investigated the impact of new motion-based video game control systems on spatial presence, perceived reality, and enjoyment of video games. In two experiments, university students played video games on either new motion-based (Sony's Move, Microsoft's Kinect, and Nintendo's Wii), or standard video game systems (PS3 and XBOX 360 with gamepads). The results indicate that, in the context of golf, racing, and boxing games, the higher technological interactivity of motion-based systems (particularly Kinect) increases feelings of spatial presence, perceived reality, and enjoyment. Perceived reality predicted spatial presence; and spatial presence, in turn, was a significant predictor of enjoyment. Moving toward a more natural user interface (NUI) between the player and the game world can create a more immersive, realistic, and fun experience for the player. A new model for enjoyment of motion-based video games is proposed.
The Role of Pulmonary Follow-up in Reducing Health Care Utilization in Infants With Bronchopulmonary Dysplasia
Authors: Rhein Lawrence M. , Konnikova Liza , McGeachey Amanda , Pruchniewski Michelle , Smith Vincent C.
Published: April 2012

Objective

To determine whether pulmonary follow-up affects rates of rehospitalization and visitations to emergency departments (EDs) in preterm infants with bronchopulmonary dysplasia (BPD).

Methods

In this retrospective cohort study, the authors identified all preterm infants born at ≤32 weeks’ gestation with at least one outpatient visit to a pulmonary follow-up clinic at Children’s Hospital Boston or a high-risk primary neurodevelopmental follow-up clinic for preterm infants. ED visits and rehospitalizations were identified through electronic medical records.

Results

Infants with pulmonary follow-up compared with infants without pulmonary follow-up were, respectively, younger (mean gestational age 26.3 ± 2.3 vs 28.3 ± 2.3 weeks, P < .0001), smaller at birth (birth weight <1200 g, 87.6% vs 57.2%, P < .0001), and needed more supplemental oxygen (55.7% vs 2.6%, P < .0001) and diuretics (65.8% vs 4.7%, P < .001) at the time of discharge from the neonatal intensive care unit. Although rates of rehospitalization were higher in infants with pulmonary follow-up, rates of visits to an ED for respiratory causes were not statistically significant. After controlling for baseline differences in both groups, the rates of rehospitalization or ED visits were the same for both groups.

Conclusions

Despite differences in lung disease status in infants with and without pulmonary follow-up, the rates of health care utilization were the same in both groups. Pulmonary follow-up may decrease the expected higher rates of ED visits and hospitalizations in preterm infants with more severe lung disease.