bluuebunny/crossref_metadata_2025 huggingface dataset:
The factor structure of the Strengths and Difficulties Questionnaire (SDQ) in Greek adolescents
Authors: Giannakopoulos George , Tzavara Chara , Dimitrakaki Christine , Kolaitis Gerasimos , Rotsika Vasiliki , Tountas Yannis
Published: August 2009

Background

The Strengths and Difficulties Questionnaire (SDQ) is a practical, economic and user-friendly screening instrument of emotional and behavioural problems in children and adolescents. This study was aimed primarily at evaluating the factor structure of the Greek version of the SDQ.

Methods

A representative nationwide sample of 1,194 adolescents (11 to 17 years old) completed the questionnaire. Confirmatory factor analysis (CFA) was conducted to assess the factor structure of the SDQ.

Results

CFA supported the original five-factor structure. The modification of the model provided some improvements. Internal consistency was acceptable for total difficulties, emotional symptoms and prosocial behaviour scale, moderate for hyperactivity/inattention scale and inadequate for peer and conduct problems scale. Older adolescents (aged 15 to 17 years) reported more hyperactivity/inattention and conduct problems than younger ones (aged 11 to 14 years) and girls reported more emotional symptoms and less prosocial behaviour problems than boys. Adolescents of low socioeconomic status (SES) reported more difficulties than those of medium and high SES.

Conclusion

The Greek SDQ could be potentially considered as a community-wide screening instrument for adolescents' emotional and behavioural problems.
Restoring Endocrine Response in Breast Cancer Cells by Inhibition of the Sphingosine Kinase-1 Signaling Pathway
Authors: Sukocheva Olga , Wang Lijun , Verrier Emily , Vadas Mathew A. , Xia Pu
Published: August 2009

We previously demonstrated that sphingosine kinase-1 (SphK1) is an important mediator in the cytoplasmic signaling of estrogens, including Ca2+ mobilization, ERK1/2 activation, and the epidermal growth factor receptor transactivation. Here we report for the first time that SphK1 activity is causally associated with endocrine resistance in MCF-7 human breast cancer cells. Enforced overexpression of human SphK1 in MCF-7 cells resulted in enhanced cell proliferation and resistance to tamoxifen-induced cell growth arrest and apoptosis. Tamoxifen-resistant (TamR) MCF-7 cells selected by prolonged exposure to 4-hydroxytamoxifen, exhibited higher levels in SphK1 expression and activity, compared with the control cells. Inhibition of SphK1 activity by either specific pharmaceutical inhibitors or the dominant-negative mutant SphK1G82D restored the antiproliferative and proapoptotic effects of tamoxifen in the TamR cells. Furthermore, silencing of SphK1, but not SphK2, expression by the specific small interference RNA also restored the tamoxifen responsiveness in the TamR cells. Thus, blockade of the SphK1 signaling pathway may reprogram cellular responsiveness to tamoxifen and abrogate antiestrogen resistance in human breast cancer cells.
The conserved metalloprotease invadolysin localizes to the surface of lipid droplets
Authors: Cobbe Neville , Marshall Kathryn M. , Rao Shubha Gururaja , Chang Ching-Wen , Di Cara Francesca , Duca Edward , Vass Sharron , Kassan Adam , Heck Margarete M. S.
Published: August 2009

Invadolysin is a metalloprotease conserved in many different organisms, previously shown to be essential in Drosophila with roles in cell division and cell migration. The gene seems to be ubiquitously expressed and four distinct splice variants have been identified in human cells but not in most other species examined. Immunofluorescent detection of human invadolysin in cultured cells reveals the protein to be associated with the surface of lipid droplets. By means of subcellular fractionation, we have independently confirmed the association of invadolysin with lipid droplets. We thus identify invadolysin as the first metalloprotease located on these dynamic organelles. In addition, analysis of larval fat-body morphological appearance and triglyceride levels in the Drosophila invadolysin mutant suggests that invadolysin plays a role in lipid storage or metabolism.
Desmethylclomipramine induces the accumulation of autophagy markers by blocking autophagic flux
Authors: Rossi Mario , Munarriz Eliana Rosa , Bartesaghi Stefano , Milanese Marco , Dinsdale David , Guerra-Martin Maria Azucena , Bampton Edward T. W. , Glynn Paul , Bonanno Giambattista , Knight Richard A. , Nicotera Pierluigi , Melino Gerry
Published: August 2009

Alterations in the autophagic pathway are associated with the onset and progression of various diseases. However, despite the therapeutic potential for pharmacological modulators of autophagic flux, few such compounds have been characterised. Here we show that clomipramine, an FDA-approved drug long used for the treatment of psychiatric disorders, and its active metabolite desmethylclomipramine (DCMI) interfere with autophagic flux. Treating cells with DCMI caused a significant and specific increase in autophagosomal markers and a concomitant blockage of the degradation of autophagic cargo. This observation might be relevant in therapy in which malignant cells exploit autophagy to survive stress conditions, rendering them more susceptible to the action of cytotoxic agents. In accordance, DCMI-mediated obstruction of autophagic flux increased the cytotoxic effect of chemotherapeutic agents. Collectively, our studies describe a new function of DCMI that can be exploited for the treatment of pathological conditions in which manipulation of autophagic flux is thought to be beneficial.
Axonal targeting of Caspr2 in hippocampal neurons via selective somatodendritic endocytosis
Authors: Bel Christophe , Oguievetskaia Ksénia , Pitaval Christophe , Goutebroze Laurence , Faivre-Sarrailh Catherine
Published: August 2009

Contactin-associated protein 2 (Caspr2) is a neuronal membrane protein that is mutated in autism and related disorders. Although it is highly enriched at juxtaparanodes of Ranvier where it is essential for Shaker-type K+ channel clustering, little is known about its function and regulation. In the present study, we examined the polarized expression of Caspr2 in hippocampal neurons using extracellular hemagglutinin (HA)-tagged Caspr2 constructs. We found that Caspr2 was targeted to the axonal surface, but colocalized with early endosomes in the somatodendritic compartment. The inhibition of endocytosis using a Dynamin-1 mutant or treatment with Dynasore prevented Caspr2 internalization from the dendrites and cell body. We identified a short sequence included into the 4.1B-binding domain that is required for the endocytosis of Caspr2. This sequence contains a protein kinase C (PKC) substrate motif on Thr1292, and point mutation of this residue or treatment with a PKC inhibitor prevented the somatodendritic internalization of Caspr2. Thus, the PKC-dependent trafficking of Caspr2 underlies its polarized expression in hippocampal neurons.
A non-contact chuck using ultrasonic vibration: Analysis of the primary cause of the holding force acting on a floating object
Authors: Yoshimoto S , Sekine H , Miyatake M
Published: August 2009

It is experimentally known that when a flat surface vibrates vertically at ultrasonic frequencies, both vertical and horizontal forces act on an object placed on the vibrating surface, enabling the vibrating surface to support an object vertically and horizontally without any contact. However, the cause of the horizontal force (called ‘the holding force’ in this article) has not been clarified yet. This article investigates experimentally and numerically the cause of the holding force generated by a vibrating surface. In numerical calculations, computational fluid dynamics was used to obtain the pressure distribution of air surrounding the floating object and the vibrating surface. It was consequently found that the holding force acting on the floating object is due to a negative average pressure generated at the edge of the object floating on the vibrating flat surface.
Analysis of a test rig drive for air springs
Authors: Okorn I , Fajdiga M , Nagode M
Published: August 2009

To determine the life of air springs, a new test rig enabling dynamic sinusoidal loading of air springs has been developed. The test rig enables the adjustment of air spring deformation and load frequency, as well as the adjustment of its geometry to different sizes of air springs. Four air springs are tested simultaneously. Between the phases of loading the air spring some time delay occurs, which is why the work that the air spring returns into the drive system during its unloading is consumed as well. The concept of the test rig and the possibilities of adjustments are presented. In order to carry out a dynamic analysis of the drive and determine the load on test rig elements, a computer program has been developed that enables the calculation of the forces, torques, and power of the driving motor for different sizes of air springs and various testing conditions. The algorithms that the program is based on and the characteristic results of the calculations are presented. Also, a comparison of energy consumption for the test of one, two, and four air springs is shown. The advantages of the new test rig as compared to other test rigs are discussed, too.
Damping force characteristics of electrorheological shock absorbers with different electrode designs
Authors: Han Y-M , Seong M-S , Choi S-B , Wereley N M
Published: August 2009

This article presents the effect of electrode design parameters on the damping force of an electrorheological (ER) shock absorber for passenger vehicles. As a first step, an ER fluid is synthesized by dispersing arabic gum particles into non-conducting oil, and its field-dependent Bingham characteristics are experimentally evaluated. The Bingham model of the ER fluid is then formulated and incorporated with the governing equations of motion of the ER shock absorber. Subsequently, several ER shock absorbers are designed and manufactured with various electrode designs, which have three different electrode gaps, lengths, and materials, respectively. The field-dependent damping force of the manufactured shock absorbers is demonstrated in the time domain and compared with simulation results. In addition, the vibration control performance of a quarter-car suspension system is presented and compared with different electrode gaps and lengths.
Investigation of wet steam flow in a 300 MW direct air-cooling steam turbine. Part 2: Flow field and windage
Authors: Cai X , Niu F , Li J , Su M , Ning T , Song Y , Wu G
Published: August 2009

The direct air-cooling steam turbine has been more and more widely used due to global climatic change. For investigating the properties of the wet steam flow in an LP direct air-cooling steam turbine, measurements with an optical—pneumatic probe were carried out in a 300 MW turbine. Part 1 of this article presents the measurement results of wetness, size distribution of fine droplets, and other information. In this part, the flow field, including the yaw angle, pitch angle, Mach number, and velocity in different backpressures are presented. Due to higher backpressure, windage occurs much more in direct air-cooling steam turbines. The flow field and wetness in windage were investigated and measurement results are presented.
Pneumocystis-associated organizing pneumonia as a manifestation of immune reconstitution inflammatory syndrome in an HIV-infected individual with a normal CD4+ T-cell count following antiretroviral therapy
Authors: Mori S , Polatino S , Estrada-Y-Martin R M
Published: August 2009

We describe a rare case of Pneumocystic jirovecii-associated organizing pneumonia (PJP) in an HIV-infected individual on highly active antiretroviral therapy (HAART) with a CD4+ T-cell count of 835 × 103 cells/mL and a low viral load. PJP was confirmed using transbronchial biopsies and bronchoalveolar lavage. The presentation in this patient suggests immune reconstitution inflammatory syndrome (IRIS) after institution of antiretroviral therapy (ART). This case report, however, is the first documented presentation of PJP in a patient with CD4 count greater than 300 prior to the induction of HAART who developed PJP and organizing pneumonia as a manifestation of IRIS. This suggests that there is continuing immune dysfunction in the face of re-expansion of CD4+ T-cells and low viral load in HIV patients despite ART.
Brain abscess due to viridans streptococci in a severely immunosuppressed HIV-infected patient
Authors: Vidal J E , Tuon F F
Published: August 2009

We report a case of viridans streptococcus brain abscess in a severely immunosuppressed HIV-infected patient with a history of chronic sinusitis. A 39-year-old homosexual man showed mental confusion and worsening of a frontal brain lesion after two weeks with antitoxoplasma therapy. Empiric treatment for central nervous system tuberculosis and pyogenic brain abscess was started. He underwent surgical drainage and the diagnosis of brain abscess due to viridans streptococci was confirmed. All empiric treatments were stopped and ceftriaxone was used for eight weeks, showing complete clinical and radiological resolution. Although infrequent, viridans streptococci, a common pyogenic aetiology of brain abscess in immunocompetent patients, should be considered in the differential diagnosis of brain lesions in AIDS patients.
Is it recurrent cryptococcal meningitis or immune reconstitution inflammatory syndrome?
Authors: Lodha A , Haran M
Published: August 2009

We report a case of a 45-year-old patient with a history of cryptococcal meningitis who was started on antiretroviral therapy. The patient presented four months later with complaints of fever and memory loss. Lumbar puncture revealed positive cryptococcal antigen and therefore the patient was treated for recurrent cryptococcal meningitis. Unfortunately, the patient did not improve even after two weeks. The diagnosis of immune reconstitution was made at this time and steroids were started. The patient showed remarkable improvement.
Audit of early syphilis: Teesside experience 2005–2007
Authors: Tayal S , Ahmed M S , Hanif U
Published: August 2009

A retrospective audit of all cases of early syphilis seen in genitourinary (GU) medicine clinics in Teesside was undertaken between 2005 and 2007. In all 80 patients early syphilis was identified. Data on patient sexuality, treatment, and serological follow-up and partner notification were collected and analysed. There were 48 heterosexual cases. There were 21 heterosexual males, and of the 27 females, 12 (44%) were diagnosed during antenatal care. Intramuscular injections of benzathine penicillin were used to treat 75 out of the 80 patients at the clinics. The remaining five patients received oral therapy for two weeks: four had a course of doxycycline and one received amoxicillin plus probenecid. The treatment rate of the population was 100%. In total, there were 115 contactable partners, of whom 87 (75.7%) were screened and/or treated. Successful treatment was defined as a four-fold or greater titre decrease in the Venereal Disease Reference Laboratory test within 3–6 months after treatment. Twenty-one patients were excluded when assessing this due to incomplete serological follow-up. Satisfactory titre declines occurred in 56 (94.9%) of the 59 patients. Overall, the clinics were shown to have adhered well with national standards. The rise in heterosexual and antenatal incidence is of concern.
Risk behaviours in HIV-positive men who have sex with men participating in an intervention in a primary care setting
Authors: Bachmann L H , Grimley D M , Chen H , Aban I , Hu J , Zhang S , Waithaka Y W , Hook E W
Published: August 2009

Men who have sex with men receiving HIV care reported their sexual behaviours and their intentions, classified according to the Transtheoretical Model of Change, to modify the following behaviours: (1) condom use by partner type and activity type; (2) reduction of partner number; and (3) disclosure of HIV serostatus to partners. Most participants were white (68.8%) or black (29.5%) and were more likely to report unprotected sex with HIV-positive than with serodiscordant partners for most activities. Whites reported more partners than black patients (mean 4.1 versus 2; P < 0.0001) and black participants reported fewer HIV-negative ( P = 0.0084) and -unknown status partners ( P = 0.00095) than whites. Cocaine/crack use was associated with more sexual partners ( P = 0.001) and more frequent unprotected sex with HIV-negative or -unknown status partners ( P = 0.036). Readiness to change risk behaviour varied by partner status and type of sexual activity. Understanding patients' risks and their readiness to change behaviours may help providers to promote sexual health.
Achieving successful partner notification: putting together the pieces of the puzzle
Authors: Estcourt C S , Sutcliffe L J , Shackleton T
Published: August 2009

Partner notification as a public health measure to reduce transmission of sexually transmitted infections (STIs) is a cornerstone of STI control in most countries. The success of any partner notification strategy is conditional on its acceptability and feasibility to both patients and health-care professionals, its compliance with relevant professional and legislative guidance, and its cost-effectiveness.
Case Study of the Development in Kenya of the Third Generation Kijito Windpump
Authors: Harries Mike
Published: August 2009

The Harries family came to Kenya in 1904 and settled on land north of Nairobi, where they farm until the present day. Whilst flying for a Christian Medical Mission in the early 1970's, Mike discovered how crucial water was to the prevention of Trachoma. This got him thinking about the problem of reliable water supplies in remote areas, and windpower seemed to be an appropriate solution. With various development partners the Harries family has spent the last 30 years, developing a wind range of Windpumps under the Trade Mark “Kijito”, and have to date installed 400 windpumps, of which 100 have been exported. The design does not use castings or gears, and is therefore suitable for manufacture in a relatively simple workshop in developing countries. With the current situation in fossil fuel supply BHEL are now seriously considering venturing into power generation, as well as a dual purpose Kijito and going back to grinding grain with wind.
Using the IEC Simple Load Model for Small Wind Turbines
Authors: Wood David
Published: August 2009

This paper describes the application of the “Simple Load Model” of the new IEC standard for the safety of small wind turbines to a three-bladed, 2m diameter, 500 W turbine with a permanent magnet generator and a furling tail fin. The two most important load cases are discussed in detail along with the determination of the component stresses from these loads. A spreadsheet is presented that allows rapid calculation of the loads and stresses for all ten cases in the Simple Load Model. The spreadsheet can be used for any small turbine. A number of inconsistencies and inaccuracies in the standard are identified; the prime one being the lack of a thrust term in the equation for the blade root bending moment. Important aspects of small wind turbine behaviour are still not well understood: these include yaw behaviour, in particular the maximum yaw rate that determines the gyroscopic moment on the blades and main shaft which is usually the dominant load on a small turbine.
Starting a Wind Turbine Business in Nepal — Case Study of the Kathmandu Alternative Power and Energy Group Pvt Ltd (KAPEG)
Authors: Freere P. , Lamichhane C. , Shrestha G. , Ghimire P. , Sharma R. , Sinha R. , Acharya P.
Published: August 2009

The general issues of starting and operating a wind turbine business in Nepal are presented, together with explanation of the effects of the culture, economic and political situation. Practical solutions are discussed as well as the legal and administrative arrangements required to operate the business. The effects of the geographical location on the business are illustrated, together with the impact of a low technical base. These issues will be shown to form a basis of an opportunity for business and social cohesion. Staffing issues are drawn upon to show how a business can have a beneficial effect on the development process of an area. With little government direction of the economy or higher education, considerable efforts in staff training is required. KAPEG's development of its wind energy business is explained with details about how international assistance is instrumental to this industrial development process.
Development of a Bamboo-Based Composite as a Sustainable Green Material for Wind Turbine Blades
Authors: Holmes John W. , Brøndsted Povl , Sørensen Bent F. , Jiang Zehui , Sun Zhengjun , Chen Xuhe
Published: August 2009

Bamboo has many engineering and environmental attributes that make it an attractive material for utilization in wind turbine blades. This paper examines the mechanical properties of a novel bamboo-poplar epoxy laminate which is being developed for wind turbine blades. Information provided in this paper includes an overview of the laminate construction and initial data for the monotonic tensile and compressive stress-strain behavior and tension-tension fatigue life of panels formed by hot-pressing. In addition, a discussion of fracture resistance of the bamboo-poplar laminate, under Mode I and Mode II loading conditions is provided.
Climate Vulnerability and the Indispensable Value of Industrial Capitalism
Authors: Lockitch Keith H.
Published: August 2009

It is widely believed that man-made greenhouse gas emissions are increasing overall vulnerability to climate-related disasters, and that, consequently, policies aimed at cutting off these emissions are urgently needed. But a broader perspective on climate vulnerability suggests that the most important factors influencing susceptibility to climate-related threats are not climatologic, but political and economic. The dramatic degree to which industrial development under capitalism has reduced the risk of harm from severe climate events in the industrialized world is significantly under-appreciated in the climate debate. Consequently, so too is the degree to which green climate and energy policies would undermine the protection that industrial capitalism affords—by interfering with individual freedoms, distorting market forces, and impeding continued industrial development and economic growth. The effect of such policies would, ironically, be a worsening of overall vulnerability to climate.
Solution of the Parallel sheaR Layer Green's Function Using Conservation Equations
Authors: Afsar M. Z.
Published: August 2009

A parallel shear flow representation of a jet is a standard way to solve for the wave propagation terms in jet noise modeling using the acoustic analogy. In this paper we show by introducing a new primary Green's function variable, proportional to the convective derivative of the pressure-like Green's function, the wave propagation equations reduce to an exact conservation form that does not include any derivatives of the mean flow. We analyze this Green's function variable numerically and show its utility when the mean flow is defined by a CFD solution and known only at a discrete set of points.
Trans-Situated Learning: Supporting a Network of Practice with an Information Infrastructure
Authors: Vaast Emmanuelle , Walsham Geoff
Published: August 2009

This paper investigates the practice-based learning dynamics that emerge among peers who share occupational practices but do not necessarily work with each other or even know each other because of geographical or organizational distance. To do so, it draws on the literatures on situated learning, networks of practice, and information infrastructures, and on insights from a longitudinal case study of the implementation of a Web-based information system used by people working in the field of environmental health. The system was deeply involved in the transformations of local practices as well as relationships between peers. Based on a dialogue between existing literatures and observations from the case study, this research extends the practice-based perspective on learning to the computer-mediated context of a network of practice. To that effect, it proposes a model of what we call trans-situated learning that is supported by the local universality of an information infrastructure whose use becomes embedded with other infrastructures.
A Control Theory Perspective on Agile Methodology Use and Changing User Requirements
Authors: Maruping Likoebe M. , Venkatesh Viswanath , Agarwal Ritu
Published: August 2009

In this paper, we draw on control theory to understand the conditions under which the use of agile practices is most effective in improving software project quality. Although agile development methodologies offer the potential of improving software development outcomes, limited research has examined how project managers can structure the software development environment to maximize the benefits of agile methodology use during a project. As a result, project managers have little guidance on how to manage teams who are using agile methodologies. Arguing that the most effective control modes are those that provide teams with autonomy in determining the methods for achieving project objectives, we propose hypotheses related to the interaction between control modes, agile methodology use, and requirements change. We test the model in a field study of 862 software developers in 110 teams. The model explains substantial variance in four objective measures of project quality—bug severity, component complexity, coordinative complexity, and dynamic complexity. Results largely support our hypotheses, highlighting the interplay between project control, agile methodology use, and requirements change. The findings contribute to extant literature by integrating control theory into the growing literature on agile methodology use and by identifying specific contingencies affecting the efficacy of different control modes. We discuss the theoretical and practical implications of our results.
Crossing Spatial and Temporal Boundaries in Globally Distributed Projects: A Relational Model of Coordination Delay
Authors: Cummings Jonathon N. , Espinosa J. Alberto , Pickering Cynthia K.
Published: August 2009

In globally distributed projects, members have to deal with spatial boundaries (different cities) and temporal boundaries (different work hours) because other members are often in cities within and across time zones. For pairs of members with spatial boundaries and no temporal boundaries (those in different cities with overlapping work hours), synchronous communication technologies such as the telephone, instant messaging (IM), and Web conferencing provide a means for real-time interaction. However, for pairs of members with spatial and temporal boundaries (those in different cities with nonoverlapping work hours), asynchronous communication technologies, such as e-mail, provide a way to interact intermittently. Using survey data from 675 project members (representing 5,674 pairs of members) across 108 projects in a multinational semiconductor firm, we develop and empirically test a relational model of coordination delay. In our model, the likelihood of delay for pairs of members is a function of the spatial and temporal boundaries that separate them, as well as the communication technologies they use to coordinate their work. As expected, greater use of synchronous web conferencing reduces coordination delay for pairs of members in different cities with overlapping work hours relative to pairs of members with nonoverlapping work hours. Unexpectedly, greater use of asynchronous e-mail does not reduce coordination delay for pairs of members in different cities with nonoverlapping work hours, but rather reduces coordination delay for those with overlapping work hours. We discuss the implications of our findings that temporal boundaries are more difficult to cross with communication technologies than spatial boundaries.
Exploring Agility in Distributed Information Systems Development Teams: An Interpretive Study in an Offshoring Context
Authors: Sarker Saonee , Sarker Suprateek
Published: August 2009

Agility is increasingly being seen as an essential element underlying the effectiveness of globally distributed information systems development (ISD) teams today. However, for a variety of reasons, such teams are often unable develop and enact agility in dealing with changing situations. This paper seeks to provide a deeper understanding of agility through an intensive study of the distributed ISD experience in TECHCOM, an organization widely recognized for its excellence in IT development and use. The study reveals that agility should be viewed as a multifaceted concept having three dimensions: resource, process, and linkage. Resource agility is based on the distributed development team's access to necessary human and technological resources. Process agility pertains to the agility that originates in the team's systems development method guiding the project, its environmental scanning, and sense-making routines to anticipate possible crises, and its work practices enabling collaboration across time zones. Linkage agility arises from the nature of interactional relationships within the distributed team and with relevant project stakeholders, and is composed of cultural and communicative elements. The paper highlights some of the difficulties in developing agility in distributed ISD settings, provides actionable tactics, and suggests contingencies wherein different facets of agility may become more (or less) critical.
The Association of Medicare Drug Coverage with Use of Evidence-Based Medications in the Veterans Health Administration
Authors: Johnson Michael L , Petersen Laura A , Sundaravaradan Raji , Byrne Margaret M , Hasche Jennifer C , Osemene Nora I , Wei Iris I , Morgan Robert O
Published: August 2009

Background:

Veterans with Medicare managed-care plans have access to pharmacy benefits outside the Veterans Health Administration (VA), but how this coverage affects use of medications for specific disease conditions within the VA is unclear.

Objective:

To examine patterns of pharmacotherapy among patients with diabetes mellitus, ischemic heart disease, and chronic heart failure enrolled in fee-for-service (FFS) or managed-care (HMO) plans and to test whether pharmacy benefit coverage within Medicare is associated with the receipt of evidence-based medications in the VA.

Methods:

A retrospective analysis of veterans dually enrolled in the VA and Medicare healthcare systems was conducted. We used VA and Medicare administrative data from 2002 in multivariable logistic regression analysis to determine the unique association of enrollment in Medicare FFS or managed-care plans on the use of medications, after adjusting for sociodemographic, geographic, and patient clinical factors.

Results:

A total of 369,697 enrollees met inclusion criteria for diabetes, ischemic heart disease, or chronic heart failure. Among patients with diabetes, adjusted odds ratios (ORs) of receiving angiotensin-converting enzyme (ACE) inhibitors and oral hypoglycemics in the FFS group were, respectively, 0.86 and 0.80 (p < 0.001). Among patients with ischemic heart disease, FFS patients were generally less likely to receive ß-blockers, antianginals, and statins. Among patients with chronic heart failure, adjusted ORs of receiving ACE inhibitors, angtotensin-receptor blockers, and statins in the FFS group were, respectively, 0.90, 0.78, and 0.79 (all p < 0.05). There were few systematic differences within HMO coverage levels.

Conclusions:

FFS-enrolled veterans were generally less likely to be receiving condition-related medications from the VA, compared with HMO-enrolled veterans with lower levels of prescription drug coverage. Pharmacy prescription coverage within Medicare affects the use of evidence-based medications for specific disease conditions in the VA.
Selective attention for masked and unmasked emotionally toned stimuli: Effects of trait anxiety, state anxiety, and test order
Authors: Edwards Mark S. , Burt Jennifer S. , Lipp Ottmar V.
Published: August 2009

We investigated selective attention for masked and unmasked, threat, and positively valenced words, in high trait anxious (HTA) and low trait anxious (LTA) individuals using the emotional Stroop colour‐naming task. State anxiety was varied within participants through the threat of electric shock. To investigate whether the sequencing of the state anxiety manipulation affected colour‐naming latencies, the ordering of the shock threat and shock safe conditions was counterbalanced across participants. The results indicated that the ordering of the state anxiety manipulation moderated masked and unmasked threat bias effects. Specifically, relative to LTA individuals, HTA individuals showed a threat interference effect, but this effect was limited to those who performed under the threat of shock in the later stages of the experiment. Irrespective of exposure mode and state anxiety status, all individuals showed interference for threat in the early stages of the experiment, relative to a threat facilitation effect in the later stages of the experiment. For the unmasked trials alone, the data also revealed a significant threat interference effect for the HTA group relative to the LTA group in the shock threat condition, and this effect was evident irrespective of shock threat order. The results are discussed with respect to the automatic nature of emotional processing in anxiety.
Fluorescence of oligonucleotides adsorbed onto the thermoresponsive poly(isopropyl acrylamide) shell of polymer nanoparticles: Application to bioassays
Authors: Martinho José M. G. , Prazeres Telmo J. V. , Moura Leila , Farinha José P. S.
Published: August 2009

The fluorescence of a rhodamine X dye covalently linked to the 5' terminus of a 25-mers thymine oligodeoxynucleotide (dT25-ROX), adsorbed on the shell of thermoresponsive core-shell polymer particles, was used to probe the polarity, mobility, and distribution of the oligodeoxynucleotides (ODNs) in the shell. The particles have a glassy core of poly(methyl methacrylate) (PMMA) with a 67-nm radius, and a thermoresponsive shell of poly(N-isopropyl acrylamide) (PNIPAM) whose thickness changes from 42 nm at 11 ºC to 5 nm at 45 ºC. The variation in polarity of the shell with temperature was obtained both from the lifetimes and from the solvatochromic shifts of the dye and shows a sharp transition at the volume phase transition temperature (T
VPT) of the PNIPAM shell. Förster resonance energy transfer (FRET) between dT25-ROX and a malachite green (MG)-labeled ODN (dT25-MG) was used to obtain the distribution of the ODNs in the thermoresponsive shell. Our results show that at 23 ºC (below T
VPT) the ODNs are distributed inside the shell, sensing an environment similar to water. At this temperature, the PNIPAM shell is composed of hydrated chains with high mobility, as probed by the fluorescence anisotropy of dT25-ROX. By increasing the temperature above T
VPT, the shell collapses and the chain mobility drastically slows down owing to the anchoring of the ODN to the dense shell of PNIPAM. Furthermore, FRET shows that the ODNs are absorbed on the 5-nm-thick collapsed shell but extend into the water. The polarity probed by the ROX averages the dyes distributed in the interior of the particle shell and in water, with 60 % of the dyes outside the particle shell (i.e., sensing pure water). Another indication that above the T
VPT most of the ODNs are oriented with the dye toward the water phase is that the mobility of the dye covalently bound to the ODNs is identical in water and in the collapsed particle shell. The hybridization efficiency between an ODN supported in the particle shell (by adsorbing the ODN below T
VPT and subsequently increasing the temperature above T
VPT) and the complementary ODN in solution is identical to that of hybridization in water. This result opens good perspectives toward the use of the core-shell thermoresponsive nanoparticles as supports in DNA bioassays.
Human Hippocampal CA1 Involvement during Allocentric Encoding of Spatial Information
Authors: Suthana Nanthia A. , Ekstrom Arne D. , Moshirvaziri Saba , Knowlton Barbara , Bookheimer Susan Y.
Published: August 2009

A central component of our ability to navigate an environment is the formation of a memory representation that is allocentric and thus independent of our starting point within that environment. Computational models and rodent electrophysiological recordings suggest a critical role for the CA1 subregion of the hippocampus in this type of coding; however, the hippocampal neural basis of spatial learning in humans remains unclear. We studied subjects learning virtual environments using high-resolution functional magnetic resonance imaging (1.6 mm × 1.6 mm in-plane) and computational unfolding to better visualize substructural changes in neural activity in the hippocampus. We show that the right posterior CA1 subregion is active and positively correlated with performance when subjects learn a spatial environment independent of starting point and direction. Altogether, our results demonstrate that the CA1 subregion is involved in our ability to learn a map-like representation of an environment.
Modulation of the Contrast Response Function by Electrical Microstimulation of the Macaque Frontal Eye Field
Authors: Ekstrom Leeland B. , Roelfsema Pieter R. , Arsenault John T. , Kolster Hauke , Vanduffel Wim
Published: August 2009

Spatial attention influences representations in visual cortical areas as well as perception. Some models predict a contrast gain, whereas others a response or activity gain when attention is directed to a contrast-varying stimulus. Recent evidence has indicated that microstimulating the frontal eye field (FEF) can produce modulations of cortical area V4 neuronal firing rates that resemble spatial attention-like effects, and we have shown similar modulations of functional magnetic resonance imaging (fMRI) activity throughout the visual system. Here, we used fMRI in awake, fixating monkeys to first measure the response in 12 visual cortical areas to stimuli of varying luminance contrast. Next, we simultaneously microstimulated subregions of the FEF with movement fields that overlapped the stimulus locations and measured how microstimulation modulated these contrast response functions (CRFs) throughout visual cortex. In general, we found evidence for a nonproportional scaling of the CRF under these conditions, resembling a contrast gain effect. Representations of low-contrast stimuli were enhanced by stimulation of the FEF below the threshold needed to evoke saccades, whereas high-contrast stimuli were unaffected or in some areas even suppressed. Furthermore, we measured a characteristic spatial pattern of enhancement and suppression across the cortical surface, from which we propose a simple schematic of this contrast-dependent fMRI response.
Otoferlin Is Critical for a Highly Sensitive and Linear Calcium-Dependent Exocytosis at Vestibular Hair Cell Ribbon Synapses
Authors: Dulon Didier , Safieddine Saaid , Jones Sherri M. , Petit Christine
Published: August 2009

Otoferlin, a C2-domain-containing Ca2+binding protein, is required for synaptic exocytosis in auditory hair cells. However, its exact role remains essentially unknown. Intriguingly enough, no balance defect has been observed in otoferlin-deficient (Otof−/−) mice. Here, we show that the vestibular nerve compound action potentials evoked during transient linear acceleration ramps inOtof−/−mice display higher threshold, lower amplitude, and increased latency compared with wild-type mice. Using patch-clamp capacitance measurement in intact utricles, we show that type I and type II hair cells display a remarkable linear transfer function between Ca2+entry, flowing through voltage-activated Ca2+channels, and exocytosis. This linear Ca2+dependence was observed when changing the Ca2+channel open probability or the Ca2+flux per channel during various test potentials. InOtof−/−hair cells, exocytosis displays slower kinetics, reduced Ca2+sensitivity, and nonlinear Ca2+dependence, despite morphologically normal synapses and normal Ca2+currents. We conclude that otoferlin is essential for a high-affinity Ca2+sensor function that allows efficient and linear encoding of low-intensity stimuli at the vestibular hair cell synapse.
Negative Guidance Factor-Induced Macropinocytosis in the Growth Cone Plays a Critical Role in Repulsive Axon Turning
Authors: Kolpak Adrianne L. , Jiang Jun , Guo Daorong , Standley Clive , Bellve Karl , Fogarty Kevin , Bao Zheng-Zheng
Published: August 2009

Macropinocytosis is a type of poorly characterized fluid-phase endocytosis that results in formation of relatively large vesicles. We report that Sonic hedgehog (Shh) protein induces macropinocytosis in the axons through activation of a noncanonical signaling pathway, including Rho GTPase and nonmuscle myosin II. Macropinocytosis induced by Shh is independent of clathrin-mediated endocytosis but dependent on dynamin, myosin II, and Rho GTPase activities. Inhibitors of macropinocytosis also abolished the negative effects of Shh on axonal growth, including growth cone collapse and chemorepulsive axon turning but not turning per se. Conversely, activation of myosin II or treatment of phorbol ester induces macropinocytosis in the axons and elicits growth cone collapse and repulsive axon turning. Furthermore, macropinocytosis is also induced by ephrin-A2, and inhibition of dynamin abolished repulsive axon turning induced by ephrin-A2. Macropinocytosis can be inducedex vivoby high Shh, correlating with axon retraction. These results demonstrate that macropinocytosis-mediated membrane trafficking is an important cellular mechanism involved in axon chemorepulsion induced by negative guidance factors.
A Functional Null Mutation ofSCN1Bin a Patient with Dravet Syndrome
Authors: Patino Gustavo A. , Claes Lieve R. F. , Lopez-Santiago Luis F. , Slat Emily A. , Dondeti Raja S. R. , Chen Chunling , O'Malley Heather A. , Gray Charles B. B. , Miyazaki Haruko , Nukina Nobuyuki , Oyama Fumitaka , De Jonghe Peter , Isom Lori L.
Published: August 2009

Dravet syndrome (also called severe myoclonic epilepsy of infancy) is one of the most severe forms of childhood epilepsy. Most patients have heterozygous mutations inSCN1A, encoding voltage-gated sodium channel Nav1.1 α subunits. Sodium channels are modulated by β1 subunits, encoded bySCN1B, a gene also linked to epilepsy. Here we report the first patient with Dravet syndrome associated with a recessive mutation inSCN1B(p.R125C). Biochemical characterization of p.R125C in a heterologous system demonstrated little to no cell surface expression despite normal total cellular expression. This occurred regardless of coexpression of Nav1.1 α subunits. Because the patient was homozygous for the mutation, these data suggest a functionalSCN1Bnull phenotype. To understand the consequences of the lack of β1 cell surface expressionin vivo, hippocampal slice recordings were performed inScn1b−/−versusScn1b+/+mice.Scn1b−/−CA3 neurons fired evoked action potentials with a significantly higher peak voltage and significantly greater amplitude compared with wild type. However, in contrast to theScn1a+/−model of Dravet syndrome, we found no measurable differences in sodium current density in acutely dissociated CA3 hippocampal neurons. WhereasScn1b−/−mice seize spontaneously, the seizure susceptibility ofScn1b+/−mice was similar to wild type, suggesting that, like the parents of this patient, one functionalSCN1Ballele is sufficient for normal control of electrical excitability. We conclude thatSCN1Bp.R125C is an autosomal recessive cause of Dravet syndrome through functional gene inactivation.
Characterizing the Appearance and Growth of Amyloid Plaques in APP/PS1 Mice
Authors: Yan Ping , Bero Adam W. , Cirrito John R. , Xiao Qingli , Hu Xiaoyan , Wang Yan , Gonzales Ernesto , Holtzman David M. , Lee Jin-Moo
Published: August 2009

Amyloid plaques are primarily composed of extracellular aggregates of amyloid-β (Aβ) peptide and are a pathological signature of Alzheimer's disease. However, the factors that influence the dynamics of amyloid plaque formation and growthin vivoare largely unknown. Using serial intravital multiphoton microscopy through a thinned-skull cranial window in APP/PS1 transgenic mice, we found that amyloid plaques appear and grow over a period of weeks before reaching a mature size. Growth was more prominent early after initial plaque formation: plaques grew faster in 6-month-old compared with 10-month-old mice. Plaque growth rate was also size-related, as smaller plaques exhibited more rapid growth relative to larger plaques. Alterations in interstitial Aβ concentrations were associated with changes in plaque growth. Parallel studies using multiphoton microscopy andin vivomicrodialysis revealed that pharmacological reduction of soluble extracellular Aβ by as little as 20–25% was associated with a dramatic decrease in plaque formation and growth. Furthermore, this small reduction in Aβ synthesis was sufficient to reduce amyloid plaque load in 6-month-old but not 10-month-old mice, suggesting that treatment early in disease pathogenesis may be more effective than later treatment. In contrast to thinned-skull windows, no significant plaque growth was observed under open-skull windows, which demonstrated extensive microglial and astrocytic activation. Together, these findings indicate that individual amyloid plaque growthin vivooccurs over a period of weeks and may be influenced by interstitial Aβ concentration as well as reactive gliosis.
Retinotopic Organization of Human Ventral Visual Cortex
Authors: Arcaro Michael J. , McMains Stephanie A. , Singer Benjamin D. , Kastner Sabine
Published: August 2009

Functional magnetic resonance imaging studies have shown that human ventral visual cortex anterior to human visual area V4 contains two visual field maps, VO-1 and VO-2, that together form the ventral occipital (VO) cluster (Brewer et al., 2005). This cluster is characterized by common functional response properties and responds preferentially to color and object stimuli. Here, we confirm the topographic and functional characteristics of the VO cluster and describe two new visual field maps that are located anterior to VO-2 extending across the collateral sulcus into the posterior parahippocampal cortex (PHC). We refer to these visual field maps as parahippocampal areas PHC-1 and PHC-2. Each PHC map contains a topographic representation of contralateral visual space. The polar angle representation in PHC-1 extends from regions near the lower vertical meridian (that is the shared border with VO-2) to those close to the upper vertical meridian (that is the shared border with PHC-2). The polar angle representation in PHC-2 is a mirror reversal of the PHC-1 representation. PHC-1 and PHC-2 share a foveal representation and show a strong bias toward representations of peripheral eccentricities. Both the foveal and peripheral representations of PHC-1 and PHC-2 respond more strongly to scenes than to objects or faces, with greater scene preference in PHC-2 than PHC-1. Importantly, both areas heavily overlap with the functionally defined parahippocampal place area. Our results suggest that ventral visual cortex can be subdivided on the basis of topographic criteria into a greater number of discrete maps than previously thought.
Muslim Indonesia's Secular Democracy
Authors: Mujani Saiful , Liddle R. William
Published: August 2009

After a decade of democracy, secular political parties dominate Muslim-majority Indonesia. Explanations include a historical pattern of religious pluralism, policies of President Suharto's New Order, creative Muslim responses to those policies, a large majority of moderate Muslim voters, and ineffective voter mobilization by Islamist parties today.