bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Intensity Pulsed Ultrasound on Tendon Healing
Authors: Fu Sai-Chuen , Shum Wai-Ting , Hung Leung-Kim , Wong Margaret Wan-Nar , Qin Ling , Chan Kai-Ming
Published: July 2008

Background

Low-intensity pulsed ultrasound has been reported to be effective in promoting tendon healing. However, its optimal time and duration has not yet been determined.

Hypothesis

Tendons at different stages of healing may respond differently to low-intensity pulsed ultrasound. In the present study, the timing effects of low-intensity pulsed ultrasound on tendon healing were investigated in a rat model with a patellar tendon graft harvest lesion.

Study Design

Controlled laboratory study.

Methods

Sixty Sprague-Dawley rats underwent central third patellar tendon donor site harvest. Low-intensity pulsed ultrasound sonication was then delivered to the injured knees at day 1, 14, or 28 after harvest for 2, 4, or 6 weeks. Tendon samples were harvested at day 14, 28, and 42 after lesion for histological examination and mechanical testing.

Results

A 2-week session of low-intensity pulsed ultrasound applied from day 1 postlesion (D1-2W) significantly improved the ultimate mechanical strength of the healing tendons from 23.1 ± 8.5 MPa to 36.6 ± 9.0 MPa. Low-intensity pulsed ultrasound did not improve healing when it was given at later stages in D15-2W and D29-2W. When low-intensity pulsed ultrasound treatment was extended from 2 weeks (D1-2W) to 4 weeks (D1-4W) or 6 weeks (D1-6W), the beneficial effects on tendon healing became insignificant. Histological examination showed that low-intensity pulsed ultrasound sonication at late healing stages may disturb remodeling with a poor collagen fiber alignment.

Conclusion

Low-intensity pulsed ultrasound promoted restoration of mechanical strength and collagen alignment in healing tendons only when applied at early healing stages.

Clinical Relevance

The present findings indicate that low-intensity pulsed ultrasound may be an effective treatment to reduce tendon donor site morbidity.
Transient Dysautonomia and Cerebellitis in Childhood Enteric Fever
Authors: Thapa Rajoo , Banerjee Pritam , Akhtar Nishar , Jain Trilochan S.
Published: July 2008

A case of childhood enteric fever complicated by transient dysautonomia and cerebellitis is reported. The child was treated with intravenous antibiotics, and the complications were managed conservatively. Dysautonomia and cerebellitis resolved by day 5 and day 8 after admission, respectively. Results of a neurologic examination at the end of 6 months were normal. Dysautonomia complicating the course of childhood enteric fever is previously unreported.
L-methylfolate in the Therapeutic Management of Major Depressive Disorder
Authors: Hunter Tracy S.
Published: July 2008

Optimal levels of the bioactive folate are necessary for maintaining proper brain and body functioning. Folate deprivation and impaired folate metabolism are clinically associated with defects in the developing nervous system. Numerous studies implicate a deficiency of bioactive folate with an increased risk of major depressive disorder and other neuropsychiatric disorders. Bioactive forms of folate, particularly L-methylfolate, have been found to augment the therapeutic efficacy of antidepressants in patients with major depressive disorder, who fail to adequately respond to standard therapies. The antidepressant action of L-methylfolate appears to improve treatment outcomes most effectively when administered as an adjuvant to traditional antidepressants. This new understanding of the role of folates in major depressive disorder and other mood disorders offers opportunities to improve treatment outcomes.
Use of Antiplatelet Agents for Primary and Secondary Prevention of Cardiovascular Disease Amongst Type 2 Diabetic Patients
Authors: Zaman Huri Hasniza , Lee Qiu Yi  , Pendek Rokiah , Che Zuraini Sulaiman
Published: July 2008

Background. A retrospective observational study was conducted to study the use of antiplatelet agents for primary and secondary prevention of cardiovascular disease among hospitalized type 2 diabetes mellitus patients.

Method. A total of 355 patients were included in the study. The compliance with the American Diabetes Association recommendation on the use of antiplatelet therapy for prevention of cardiovascular disease was studied.

Results. For the primary prevention group, type 2 diabetes mellitus, patients with known dyslipidemia were more likely to receive antiplatelet therapy than those without dyslipidemia (P = 0.023). The rate of adherence to the American Diabetes Association recommendations on the use of antiplatelet therapy for secondary prevention of cardiovascular disease was higher than for primary prevention of cardiovascular disease (P = 0.001).

Conclusion. In conclusion, many of the eligible patients still do not receive antiplatelet therapy, particularly in primary prevention of cardiovascular disease. Measures should be taken to ensure that type 2 diabetes mellitus patients receive the antiplatelet therapy and hence prevent macrovascular complications.
Palliative Management of Parkinson Disease: Focus on Nonmotor, Distressing Symptoms
Authors: Chen Jack J. , Trombetta Dominick P. , Fernandez Hubert H.
Published: July 2008

Parkinson disease is a progressive neurodegenerative disease that commonly affects elderly persons. In the absence of neuroprotective or curative therapies, currently available therapies only provide symptomatic benefit. Progression to advanced Parkinson disease is often accompanied by functional dependence with increased risk of admission to a long-term care facility. The prevalence of Parkinson disease in long-term care facilities, within the United States, has been estimated to be between 5.2% and 10%. Patients with advanced Parkinson disease also experience other distressing motor and nonmotor conditions, such as motor complications, dementia, depression, gastrointestinal distress, orthostatic hypotension, pain, and psychosis, which can be a challenge for clinicians to manage. The presence of distressing symptoms along with the fact that Parkinson disease remains incurable necessitate discussion on a palliative care approach to this disorder. This article discusses the symptomatic management of distressing symptoms encountered in the long-term care resident with Parkinson disease, including motor complications and nonmotor features.
Labour market mobility and employment security of male employees in Europe: `trade-off' or `flexicurity'?
Authors: Muffels Ruud , Luijkx Ruud
Published: July 2008

The dominant view in economics is that increasing demands for flexibility on the labour market jeopardizes employment security. However, against the prediction of a negative relationship or a`trade-off' between flexibility and security, there is evidence for a positive, mutually reinforcing relationship known as the `flexicurity' thesis. Using comparative panel data for 14 European countries, we elaborate dynamic outcome indicators for flexibility and employment security to assess the differences across countries and welfare regimes in balancing the two.We estimate transition models to explain the observed mobility patterns.The outcomes confirm the impact of the institutional set-up indicated by regime type on these transitions supporting the `variety of capitalism' approach.The regulated Southern and Continental regimes perform worst and the unregulated Anglo-Saxon and Nordic regimes best in attaining high levels of flexibility and employment security simultaneously, though for both regimes with a small loss either in flexibility or in security.
In solitary, in solidarity
Authors: Nyers Peter
Published: July 2008

This article assesses the challenges to a key 'anti-policy' within anti-terrorism: the detention of terror suspects. It analyses the global response to the 2005 kidnapping of a Christian Peacemaker Team in Iraq. Particular focus is given to how detainees in the 'War on Terror' emerged as key spokespeople in the attempt to influence the actions of the kidnappers. So-called 'terror detainees' in the UK and Canada made several appeals for mercy and wrote letters establishing their solidarity with the CPT hostages. Drawing on the political theory of Jacques Ranciere, the article analyses examples of detainee or hostage solidarity as acts of political subjectification. Detention is analysed as a site where key political dynamics are enacted. For detainees to articulate a grievance as an equal or enact an international solidarity is a radical political moment that serves to disrupt the routines and normalizations of the anti-policy of detention.
Designing for the unexpected: the role of creative group work for emerging interaction design paradigms
Authors: Pirhonen Antti , Murphy Emma
Published: July 2008

Interaction design for new technological environments relies on the tradition of human—computer interaction (HCI). With roots in the 1980s, HCI design paradigms often reflect the setting in which the user is an office worker in front of a desktop computer. As computational power can now be embedded in almost any type of product, the desktop setting has lost much of its relevance as a starting point for interface design. In particular, interfaces for wearable computing challenge designers to look for completely new approaches to interaction design. In this article, we propose a method in which the ideas for new creative forms of interaction design are triggered through panel work. This method draws on an underpinning theoretical framework from structural semiotics that emphasizes the holistic nature of design.
Wear now!
Authors: High Tea With Mrs Woo  , Cranny-Francis Anne
Published: July 2008

This is a photo-essay of the design philosophy and practice of a three-sister fashion design team based in Newcastle, Australia. Their interest in fabrication, textiles and technology in fashion led them to participate in the Australian Network of Art and Technology (ANAT)'s reSkin wearable technology laboratory 2007. The lab explored the integration of electronics and new materials into traditional craft practices and design artefacts. This photo-essay addresses questions raised by Anne Cranny-Francis that came out of that ReSkin experience, as well as general questions relating to their design practice.
After culture
Authors: Van Oord Lodewijk
Published: July 2008

This article analyses intergroup differences in education, with particular emphasis on schools offering one or more of the International Baccalaureate programmes (`IB World schools'). Experiences of human difference are often interpreted in terms of culture, and the notion of intercultural understanding is valued in many international schools. Yet intercultural encounters hardly differ from what social psychologists call `intergroup encounters'. Social identity theory explains the dynamic of these encounters more effectively than models focusing on cultural difference. With reference to the contact hypothesis, this article presents suggestions as to how international schools can capitalize on their diversity by becoming practice grounds for intergroup encounters.
Feature Selection for Robust Classification of Crack and Drop Signals
Authors: Kappatos Vassilios , Dermatas Evangelos
Published: July 2008

This paper presents a study to the problem of features selection for accurate recognition of crack signals in raining conditions, using a multilayer perceptron and a radial basis function neural network. The features extraction process is accomplished for two time frames: in the first time frame the presence of the signal reflection is minimal; in the later a wider window include signal reflections at the specimen edges. An extensive set of 90 features (41 of them are novel), 67 in the time domain and 23 in the frequency domain, are extracted from the normalized signals and are sorted according to Fisher ratio (F-ratio). The signals database consists of over than 20,000 simulated cracks and drops signals. The NNs classification accuracy of a single crack signal in rain conditions using the most robust features ranges from 80.08% to 99.08%, which remains in the same levels when white-Gaussian noise up to 0 dB signal-to-noise ratio is added to the signal.
Sensor Self-diagnosis Using a Modified Impedance Model for Active Sensing-based Structural Health Monitoring
Authors: Park Seunghee , Park Gyuhae , Yun Chung-Bang , Farrar Charles R.
Published: July 2008

The active sensing methods using piezoelectric materials have been extensively investigated for the efficient use in structural health monitoring (SHM) applications. Relying on high frequency structural excitations, the methods showed the extreme sensitivity to minor defects in a structure. Recently, a sensor self-diagnostic procedure that performs in situ monitoring of the operational status of piezoelectric (PZT) active sensors and actuators in SHM applications has been proposed. In this investigation, previously developed impedance models were revisited in order to investigate the effects of sensor and/or bonding defects on the admittance measurement. New parameters for sensor quality assessment of a PZT and coupling degradation effects between a PZT and bonding layer were incorporated into the traditional electromechanical impedance model for better estimation of the electromechanical impedance signatures and sensor diagnostics. The feasibility of the modified impedance model for sensor self-diagnosis using the admittance measurements was demonstrated by a series of parametric studies using a simple example of PZT-driven single degree of freedom spring-mass-damper system. This paper summarizes the description of the proposed modified electromechanical impedance model, parametric studies for impedance-based sensor diagnostics, and several issues that can be used as a guideline for future investigation.
Structural Damage Detection Using Auxiliary Particle Filtering Method
Authors: Songtao Xue  , Hesheng Tang  , Qiang Xie
Published: July 2008

Structural damage identification is an important objective of health monitoring for civil infrastructures. Frequently, damage to a structure may be reflected by a change of some system parameters, such as a degradation of the stiffness. In this paper, an auxiliary particle filtering (APF) method is applied to track a dynamic system with sudden parameter changes. In the APF, the importance density is proposed as a mixture density that depends upon the past state and the most recent observations, and hence which has a good time-tracking ability that is more suitable for tracking the nonstationary system than the conventional particle filters. Simulation results for tracking the sudden parameter changes of nonlinear hysteretic structures are presented to demonstrate the application and effectiveness of the proposed technique in detecting the structural damages.
Performance Evaluation and Reliable Implementation of Data Transmission for Wireless Sensors on Rotating Mechanical Structures
Authors: Lei Tang  , Wang Kuang-Ching , Yong Huang
Published: July 2008

Wireless sensors are increasingly adopted in mechanical, civil, and aerospace engineering systems to acquire and wirelessly transmit sensed information to data receivers for structural health or machine condition monitoring. Wireless data transmission performance in such engineering systems was known to depend greatly on sensor positions and possible relative motions with respect to the environment. Pronounced performance deterioration can occur under certain sensing conditions such as that of a rotating engineering structure monitoring system. Various studies have applied wireless sensors on rotating mechanical structures for condition monitoring, but a systematic study of their data transmission performance is still missing. This study is devoted to characterizing such performance of wireless sensors on a rotating lathe spindle and further examining the efficacy of a commonly adopted automatic repeat request (ARQ)-based reliable transmission method. The experimental measurements have shown that the transmission error rates were proportional to rotation speeds at certain receiver locations, while a minor change in the receiver location could significantly alter such dependency. It was found that the ARQ approach effectively assured a reliable data transmission during rotation with little retransmission overheads, and the reliable transmission throughput varied with different packet sizes and packet generation intervals.
Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation
Authors: Arulogun Suzanne O. , Prince H. Miles , Ng Jonathan , Lade Stephen , Ryan Gail F. , Blewitt Odette , McCormack Christopher
Published: July 2008

Although mycosis fungoides (MF) is typically an indolent disease, patients with advanced-stage disease (stages IIB-IVB), including Sézary syndrome (SS), often have a poor outcome. A 31-year, retrospective analysis of our cutaneous lymphoma database, of 297 patients with MF and SS, was undertaken to study long-term outcomes and identify clinical predictors of outcome in patients with advanced-stage disease (ASD, n = 92) and large cell transformation (LCT, n = 22). Two-thirds of patients with ASD presented with de novo ASD. The median overall survival (OS) for ASD was 5 years with a 10-year predicted OS of 32%. Age at initial diagnosis (P = .01), tumor stage (P = .01), and clinical stage (P = .001) were found to be significant predictors of outcome. Patients who presented with de novo ASD demonstrated better outcomes that were not statistically significant than those with a prior diagnosis of early-stage MF (P = .25). Transformation developed in 22 of the 297 MF/SS patients (7.4%), with a transformation rate of only 1.4% in patients with early-stage disease, compared with stage IIB (27%) and stage IV (56%-67%) disease. The median OS from diagnosis of LCT was 2 years. We confirm that the incidence of LCT is strongly dependent on tumor stage at diagnosis, and we demonstrate a much lower overall risk of LCT than previously reported.
The central proline rich region of POB1/REPS2 plays a regulatory role in epidermal growth factor receptor endocytosis by binding to 14-3-3 and SH3 domain-containing proteins
Authors: Tomassi Laura , Costantini Anna , Corallino Salvatore , Santonico Elena , Carducci Martina , Cesareni Gianni , Castagnoli Luisa
Published: July 2008

Background

The human POB1/REPS2 (Partner of RalBP1) protein is highly conserved in mammals where it has been suggested to function as a molecular scaffold recruiting proteins involved in vesicular traffic and linking them to the actin cytoskeleton remodeling machinery. More recently POB1/REPS2 was found highly expressed in androgen-dependent prostate cancer cell lines, while one of its isoforms (isoform 2) is down regulated during prostate cancer progression.

Results

In this report we characterize the central proline rich domain of POB1/REPS2 and we describe for the first time its functional role in receptor endocytosis. We show that the ectopic expression of this domain has a dominant negative effect on the endocytosis of activated epidermal growth factor receptor (EGFR) while leaving transferrin receptor endocytosis unaffected. By a combination of different approaches (phage display, bioinformatics predictions, peptide arrays, mutagenic analysis, in vivo co-immunoprecipitation), we have identified two closely spaced binding motifs for 14-3-3 and for the SH3 of the proteins Amphiphysin II and Grb2. Differently from wild type, proline rich domains that are altered in these motifs do not inhibit EGFR endocytosis, suggesting that these binding motifs play a functional role in this process.

Conclusion

Our findings are relevant to the characterization of the molecular mechanism underlying the involvement of POB1/REPS2, SH3 and 14-3-3 proteins in receptor endocytosis, suggesting that 14-3-3 could work by bridging the EGF receptor and the scaffold protein POB1/REPS2.
Assessing probe-specific dye and slide biases in two-color microarray data
Authors: Lu Ruixiao , Lee Geun-Cheol , Shultz Michael , Dardick Chris , Jung Kihong , Phetsom Jirapa , Jia Yi , Rice Robert H , Goldberg Zelanna , Schnable Patrick S , Ronald Pamela , Rocke David M
Published: July 2008

Background

A primary reason for using two-color microarrays is that the use of two samples labeled with different dyes on the same slide, that bind to probes on the same spot, is supposed to adjust for many factors that introduce noise and errors into the analysis. Most users assume that any differences between the dyes can be adjusted out by standard methods of normalization, so that measures such as log ratios on the same slide are reliable measures of comparative expression. However, even after the normalization, there are still probe specific dye and slide variation among the data. We define a method to quantify the amount of the dye-by-probe and slide-by-probe interaction. This serves as a diagnostic, both visual and numeric, of the existence of probe-specific dye bias. We show how this improved the performance of two-color array analysis for arrays for genomic analysis of biological samples ranging from rice to human tissue.

Results

We develop a procedure for quantifying the extent of probe-specific dye and slide bias in two-color microarrays. The primary output is a graphical diagnostic of the extent of the bias which called ECDF (Empirical Cumulative Distribution Function), though numerical results are also obtained.

Conclusion

We show that the dye and slide biases were high for human and rice genomic arrays in two gene expression facilities, even after the standard intensity-based normalization, and describe how this diagnostic allowed the problems causing the probe-specific bias to be addressed, and resulted in important improvements in performance. The R package LMGene which contains the method described in this paper has been available to download from Bioconductor.
Parallel and serial computing tools for testing single-locus and epistatic SNP effects of quantitative traits in genome-wide association studies
Authors: Ma Li , Runesha H Birali , Dvorkin Daniel , Garbe John R , Da Yang
Published: July 2008

Background

Genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) markers provide opportunities to detect epistatic SNPs associated with quantitative traits and to detect the exact mode of an epistasis effect. Computational difficulty is the main bottleneck for epistasis testing in large scale GWAS.

Results

The EPISNPmpi and EPISNP computer programs were developed for testing single-locus and epistatic SNP effects on quantitative traits in GWAS, including tests of three single-locus effects for each SNP (SNP genotypic effect, additive and dominance effects) and five epistasis effects for each pair of SNPs (two-locus interaction, additive × additive, additive × dominance, dominance × additive, and dominance × dominance) based on the extended Kempthorne model. EPISNPmpi is the parallel computing program for epistasis testing in large scale GWAS and achieved excellent scalability for large scale analysis and portability for various parallel computing platforms. EPISNP is the serial computing program based on the EPISNPmpi code for epistasis testing in small scale GWAS using commonly available operating systems and computer hardware. Three serial computing utility programs were developed for graphical viewing of test results and epistasis networks, and for estimating CPU time and disk space requirements.

Conclusion

The EPISNPmpi parallel computing program provides an effective computing tool for epistasis testing in large scale GWAS, and the epiSNP serial computing programs are convenient tools for epistasis analysis in small scale GWAS using commonly available computer hardware.
Genetic origin, admixture, and asymmetry in maternal and paternal human lineages in Cuba
Authors: Mendizabal Isabel , Sandoval Karla , Berniell-Lee Gemma , Calafell Francesc , Salas Antonio , Martínez-Fuentes Antonio , Comas David
Published: July 2008

Background

Before the arrival of Europeans to Cuba, the island was inhabited by two Native American groups, the Tainos and the Ciboneys. Most of the present archaeological, linguistic and ancient DNA evidence indicates a South American origin for these populations. In colonial times, Cuban Native American people were replaced by European settlers and slaves from Africa. It is still unknown however, to what extent their genetic pool intermingled with and was 'diluted' by the arrival of newcomers. In order to investigate the demographic processes that gave rise to the current Cuban population, we analyzed the hypervariable region I (HVS-I) and five single nucleotide polymorphisms (SNPs) in the mitochondrial DNA (mtDNA) coding region in 245 individuals, and 40 Y-chromosome SNPs in 132 male individuals.

Results

The Native American contribution to present-day Cubans accounted for 33% of the maternal lineages, whereas Africa and Eurasia contributed 45% and 22% of the lineages, respectively. This Native American substrate in Cuba cannot be traced back to a single origin within the American continent, as previously suggested by ancient DNA analyses. Strikingly, no Native American lineages were found for the Y-chromosome, for which the Eurasian and African contributions were around 80% and 20%, respectively.

Conclusion

While the ancestral Native American substrate is still appreciable in the maternal lineages, the extensive process of population admixture in Cuba has left no trace of the paternal Native American lineages, mirroring the strong sexual bias in the admixture processes taking place during colonial times.
Decision maker views on priority setting in the Vancouver Island Health Authority
Authors: Dionne Francois , Mitton Craig , Smith Neale , Donaldson Cam
Published: July 2008

Background

Decisions regarding the allocation of available resources are a source of growing dissatisfaction for healthcare decision-makers. This dissatisfaction has led to increased interest in research on evidence-based resource allocation processes. An emerging area of interest has been the empirical analysis of the characteristics of existing and desired priority setting processes from the perspective of decision-makers.

Methods

We conducted in-depth, face-to-face interviews with 18 senior managers and medical directors with the Vancouver Island Health Authority, an integrated health care provider in British Columbia responsible for a population of approximately 730,000. Interviews were transcribed and content-analyzed, and major themes and sub-themes were identified and reported.

Results

Respondents identified nine key features of a desirable priority setting process: inclusion of baseline assessment, use of best evidence, clarity, consistency, clear and measurable criteria, dissemination of information, fair representation, alignment with the strategic direction and evaluation of results. Existing priority setting processes were found to be lacking on most of these desired features. In addition, respondents identified and explicated several factors that influence resource allocation, including political considerations and organizational culture and capacity.

Conclusion

This study makes a contribution to a growing body of knowledge which provides the type of contextual evidence that is required if priority setting processes are to be used successfully by health care decision-makers.
Expression of frog virus 3 genes is impaired in mammalian cell lines
Authors: Eaton Heather E , Metcalf Julie , Brunetti Craig R
Published: July 2008

Frog virus 3 (FV3) is a large DNA virus that is the prototypic member of the family Iridoviridae. To examine levels of FV3 gene expression we generated a polyclonal antibody against the FV3 protein 75L. Following a FV3 infection in fathead minnow (FHM) cells 75L was found in vesicles throughout the cytoplasm as early as 3 hours post-infection. While 75L expressed strongly in FHM cells, our findings revealed no 75L expression in mammalian cells lines despite evidence of a FV3 infection. One explanation for the lack of gene expression in mammalian cell lines may be inefficient codon usage. As a result, 75L was codon optimized and transfection of the codon optimized construct resulted in detectable expression in mammalian cells. Therefore, although FV3 can infect and replicate in mammalian cell lines, the virus may not express its full complement of genes due to inefficient codon usage in mammalian species.
Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice
Authors: Iida Noriho , Nakamoto Yasunari , Baba Tomohisa , Kakinoki Kaheita , Li Ying-Yi , Wu Yu , Matsushima Kouji , Kaneko Shuichi , Mukaida Naofumi
Published: July 2008

The first step in the generation of tumor immunity is the migration of dendritic cells (DCs) to the apoptotic tumor, which is presumed to be mediated by various chemokines. To clarify the roles of chemokines, we induced apoptosis using suicide gene therapy and investigated the immune responses following tumor apoptosis. We injected mice with a murine hepatoma cell line, BNL 1ME A.7R.1 (BNL), transfected with HSV-thymidine kinase (tk) gene and then treated the animals with ganciclovir (GCV). GCV treatment induced massive tumor cell apoptosis accompanied with intratumoral DC infiltration. Tumor-infiltrating DCs expressed chemokine receptors CCR1 and CCR5, and T cells and macrophages expressed CCL3, a ligand for CCR1 and CCR5. Moreover, tumor apoptosis increased the numbers of DCs migrating into the draining lymph nodes and eventually generated a specific cytotoxic cell population against BNL cells. Although GCV completely eradicated HSV-tk-transfected BNL cells in CCR1-, CCR5-, or CCL3-deficient mice, intratumoral and intranodal DC infiltration and the subsequent cytotoxicity generation were attenuated in these mice. When parental cells were injected again after complete eradication of primary tumors by GCV treatment, the wild-type mice completely rejected the rechallenged cells, but the deficient mice exhibited impairment in rejection. Thus, we provide definitive evidence indicating that CCR1 and CCR5 and their ligand CCL3 play a crucial role in the regulation of intratumoral DC accumulation and the subsequent establishment of tumor immunity following induction of tumor apoptosis by suicide genes.
‘There is no outer without inner space’: constructing the haveli as home
Authors: Bryden Inga
Published: July 2008

Working within a framework of Indian architectural theory and philosophies of space, this discussion focuses on the traditional space of the courtyard house, or haveli. What is distinctive about this building architecturally, spatially, and as a Hindu domestic space? In order to respond to this question, the architectural principle Vastu Vidya is focused on since it defines the dimensions and orientation of the house, and the direction of household activities. Moreover, Vastu connects the individual body to the home, and the home to the cosmos. The article considers the design of the haveli and the history of its organization and use of space. The article particularly highlights the ways in which, if at all, the haveli has been adapted in order to accommodate modified lifestyles. The haveli, it is argued, is an ambivalent space in that it is both ‘enclosed’ and ‘open’: as such, it facilitates a flexible relation between the inhabitants and the spaces of their house, in terms of use and modernization. Furthermore, the notion that the haveli is wholly a ‘traditional’ space is problematized. The research methodology partly utilizes individual narratives and oral history, based on discussions held with mid-caste women and their families living in the old city area of Jaipur, the capital of Rajasthan, in 1999 and 2000. In this sense the article interprets individual lived experience as a geography of intimacy. The discussion focuses on a representative haveli as a case study, in order to establish it as a culturally specific space and to delineate the interaction of the inhabitants with the space of their home, whereby each changes the other. It assesses the haveli as a gendered space, and also the extent and nature of the inhabitants’ knowledge and application of Vastu.
Finding of Kinase Domain Mutations in Patients With Chronic Phase Chronic Myeloid Leukemia Responding to Imatinib May Identify Those at High Risk of Disease Progression
Authors: Khorashad Jamshid S. , de Lavallade Hugues , Apperley Jane F. , Milojkovic Dragana , Reid Alistair G. , Bua Marco , Szydlo Richard , Olavarria Eduardo , Kaeda Jaspal , Goldman John M. , Marin David
Published: July 2008

Purpose

Kinase domain (KD) mutations in the BCR-ABL gene are associated with resistance to imatinib in chronic myeloid leukemia (CML) but their incidence and prognostic significance in chronic phase (CP) patients without resistance are unclear.

Patients and Methods

We analyzed outcome for 319 patients with CML-CP who were treated with imatinib; 171 were in early CP (ECP) and 148 were in late CP (LCP). Patients were screened routinely for mutations using direct sequencing regardless of response status. The 5-year cumulative incidence of mutations was 6.6% for ECP and 17% for LCP patients.

Results

Of the 319 patients, 214 (67%) achieved complete cytogenetic responses (CCyR). The identification of a mutation without other evidence of imatinib resistance was highly predictive for loss of CCyR (RR, 3.8; P = .005) and for progression to advanced phase (RR, 2.3; P = .01), though the intervals from first identification to loss of CCyR and disease progression were relatively long (median, 21 and 16 months, respectively). Mutations in the P-loop (excluding residue 244) were associated with a higher risk of progression than mutations elsewhere.

Conclusion

We conclude that routine mutation screening of patients who appear to be responding to imatinib may identify those at high risk of disease progression.
Enabling innovation in health-care delivery
Authors: Parnaby John , Towill Denis R
Published: July 2008

Achieving lasting performance improvement in health care is a demanding challenge. Service delivery processes are frequently fragmented with many symptoms of poor behaviour observable. Competing vested interests within the National Health Service (NHS) and experiences of muddled and muddied top–down government exhortation suggest the need for a balanced perspective in which the expectations of patients, staff, management and government can be considered, agreed and enabled. Our conclusion is that effective innovation is best achieved by establishing a ‘Train-Do–Train-Do’ cycle in which all ‘players’ in the system must be actively involved. The particular methodology of ‘managing by projects’ for effective bottom–up step-by-step innovation in NHS practice is described. It takes a holistic and systematic view of health-care delivery as a service business process to be optimized via a five-step procedure. The core tool element of this methodology is the multidiscipline natural-group task force used to execute the change process in an enterprise. When properly constituted, motivated and driven, it is very capable of transforming a ‘mess’ into an effective health-care delivery process.
Using SitReps performance data to monitor the delayed discharge process
Authors: Godden Sylvia , McCoy David , Pollock Allyson M
Published: July 2008

Situation Reports (SitReps) is an internal Department of Health performance data collecting system. Although intended primarily for internal use, the data are also used to answer parliamentary questions, brief ministers and to inform national performance indicators. This paper reviews the data collection system and data-set, and shows how it can be used to evaluate delays in hospital discharge under the Community Care (Delayed Discharges etc.) Act 2003. However, limitations in the data include the fact that the data have only recently been extended to National Health Service (NHS) non-acute settings and do not include NHS patients in the private acute sector. Further, as the data-set derives from a weekly aggregate return rather than from individualized person-based records, it cannot be used to evaluate length of delay, or to link to other relevant data such as emergency readmissions. The provision of individualized data to facilitate linkage and extending coverage would increase its potential future use. Categories of delay should be further refined to facilitate monitoring of delays due to disputes about eligibility.
Revenue Ranking of Discriminatory and Uniform Auctions with an Unknown Number of Bidders
Authors: Pekeč Aleksandar Saša , Tsetlin Ilia
Published: July 2008

An important managerial question is the choice of the pricing rule. We study whether this choice depends on the uncertainty about the number of participating bidders by comparing expected revenues under discriminatory and uniform pricing within an auction model with affiliated values, stochastic number of bidders, and linear bidding strategies. We show that if uncertainty about the number of bidders is substantial, then the discriminatory pricing generates higher expected revenues than the uniform pricing. In particular, the first-price auction might generate higher revenues than the second-price auction. Therefore, uncertainty about the number of bidders is an important factor to consider when choosing the pricing rule. We also study whether eliminating this uncertainty, i.e., revealing the number of bidders, is in the seller's interests, and discuss the existence of an increasing symmetric equilibrium.
Inadequate iodine nutrition of pregnant women from Extremadura (Spain)
Authors: Sánchez-Vega Javier , Escobar del Rey Francisco , Fariñas-Seijas Humberto , Morreale de Escobar Gabriella
Published: July 2008

Objective

To evaluate the iodine nutrition of the pregnant women of the Spanish Autonomous Community Extremadura. There are ∼10 000 births per year in Extremadura, which historically contains areas with endemic goiter (Las Hurdes).

Design

Population study in which a representative sample of pregnant women of the general population was analyzed, along with another sample of pregnant women from traditionally goitrogenic areas. With the collaboration of selected health centers, an additional sample of blood and urine was obtained within the primary health care pregnancy-monitoring program; these samples were sent to a single central laboratory.

Methods

Biochemistry: determination of iodine and creatinine in urine, and serum concentrations of thyroxine, free thyroxine, tri-iodothyronine, TSH, thyroglobulin, and two anti-thyroid antibodies. Each parameter was measured by means of a single specific RIA.

Results

Changes between the first trimester and later stages of pregnancy of all biochemical variables studied corresponded with those described for other European areas with a comparable iodine nutrition. Using the urinary iodine concentration value as an indicator of iodine ingestion, it was found that in the first trimester of pregnancy six out of ten women from Extremadura ingested less than the currently recommended amount (250 μg I/day), and approximately three out of ten of these women ingested less than half of this amount.

Conclusions

It is imperative to implement in all Extremadura the generalized and controlled use of complements that contain 200–250 μg I/day throughout pregnancy and, if possible, before.
Liver Tumors in Children
Authors: Litten Jason B. , Tomlinson Gail E.
Published: July 2008

Learning Objectives

After completing this course, the reader should be able to: Describe the current epidemiologic trends in hepatoblastoma.Identify the genetic syndromes that are seen in a subset of liver tumors.Assess the need for complete tumor resection in the treatment of liver tumors in children as well as the increasingly important option of liver transplantation for those patients with unresectable tumors.Discuss the impact of the hepatitis vaccine in reducing the incidence of hepatocellular carcinoma.Explain the prognostic impact of different histologic subtypes of hepatoblastoma.Promote the need for future clinical trials in testing new agents for hepatocellular carcinoma in children.Employ the different staging systems used in liver tumors, including the traditional North American postsurgical staging system and the European presurgical staging system using imaging.

CME This article is available for continuing medical education credit at CME.TheOncologist.com.

Malignant liver tumors account for slightly >1% of all pediatric malignancies, with roughly 150 new cases of liver tumors diagnosed in the U.S. annually. The embryonal tumor, hepatoblastoma, accounts for two thirds of malignant liver tumors in children. Other liver malignancies in children include hepatocellular carcinoma, sarcomas, germ cell tumors, and rhabdoid tumors. Benign tumors of the liver in children include vascular tumors, hamartomas, and adenomas. There is an apparent increase in the incidence of hepatoblastoma with perinatal exposures and decreased premature infant mortality as postulated causes for this increased risk. The known causes and associations of liver tumors in children as well as the approaches to diagnosis and treatment of children are discussed in this review article.
Long in the tooth: evolution of sabertooth cat cranial shape
Authors: Slater Graham J. , Van Valkenburgh Blaire
Published: July 2008

Sabertooths exhibit one of the most extreme feeding adaptations seen in mammals. The functional consequences of accommodating extremely elongate upper canine teeth are severe, resulting in a well-documented suite of cranial modifications. We used geometric morphometric methods to study the evolution of overall shape in the skulls of extant and extinct feline and machairodontine felids, as well as extinct nimravids. Trends in skull evolution were evaluated by using relative warps analysis and tested for association with body size and canine tooth length. Primitive sabertooths from all lineages exhibit cranial shapes more similar to conical-toothed cats, despite the presence of moderately developed saberteeth. More-derived forms in both nimravids and felids diverge in skull morphospace to form two distinct sabertooth types (dirk-toothed and scimitar-toothed) that differ in canine shape. Skull shape in conical-toothed cats is strongly associated with body size, but not canine length. However, within each sabertooth lineage, skull shape is significantly correlated with canine length, suggesting that gape-related demands drove the evolution of sabertooth skull morphology.
The flourishing diversity of models in theoretical morphology: from current practices to future macroevolutionary and bioenvironmental challenges
Authors: Dera Guillaume , Eble Gunther J. , Neige Pascal , David Bruno
Published: July 2008

For decades, theoretical morphological studies of different groups of organisms have been successfully pursued in biological, paleontological, and computational contexts, often with distinct modeling approaches and research questions. A regular influx of new perspectives and varied expertise has contributed to the emergence of a veritable multidisciplinary outlook for theoretical morphology. The broadening of this discipline is reflected in a substantial increase in the number of models, leading to a bewildering diversity that has yet to be scrutinized. In this work, we tackle this issue in a synthetic fashion, with a quantitative meta-analysis that allows an objective comparison of theoretical morphological models treated as entities. By analogy with empirical morphospace analyses of actual organisms, we performed a multivariate ordination of a representative sample of models, producing a metaspace of models in which patterns of similarity and difference are visualized. A phenetic tree was used to characterize the relationships between models. Four major groups have been identified, and their disparity analyzed. We suggest this typology as a useful starting point to identify a core set of fundamental principles and protocols for better interpretation of the plethora of current models and for more efficient construction of models in the future. This in turn can help in diversifying the scope of macroevolutionary, developmental, and bioenvironmental questions in theoretical morphology.
Diazoxide-induced β-cell rest reduces endoplasmic reticulum stress in lipotoxic β-cells
Authors: Sargsyan Ernest , Ortsäter Henrik , Thorn Kristofer , Bergsten Peter
Published: July 2008

Elevated levels of glucose and lipids are characteristics of individuals with type 2 diabetes mellitus (T2DM). The enhanced nutrient levels have been connected with deterioration of β-cell function and impaired insulin secretion observed in these individuals. A strategy to improve β-cell function in individuals with T2DM has been intermittent administration of KATP channel openers. After such treatment, both the magnitude and kinetics of insulin secretion are markedly improved. In an attempt to further delineate mechanisms of how openers of KATP channels improve β-cell function, the effects of diazoxide on markers of endoplasmic reticulum (ER) stress was determined in β-cells exposed to the fatty acid palmitate. The eukaryotic translation factor 2-alpha kinase 3 (EIF2AK3; also known as PERK) and endoplasmic reticulum to nucleus signaling 1 (ERN1; also known as IRE1) pathways, but not the activating transcription factor (ATF6) pathway of the unfolded protein response, are activated in such lipotoxic β-cells. Inclusion of diazoxide during culture attenuated activation of the EIF2AK3 pathway but not the ERN1 pathway. This attenuation was associated with reduced levels of DNA-damage inducible transcript 3 (DDIT3; also known as CHOP) and β-cell apoptosis was decreased. It is concluded that reduction of ER stress may be a mechanism by which diazoxide improves β-cell function.
Citizens, consumers and the acceptability of road pricing
Authors: Halden D.
Published: July 2008

Although road pricing has been shown to provide overall benefits to both the economy and society, widespread public acceptance has remained elusive. By drawing from recent transport research, this paper analyses the conflicts which people face between their desire to be good citizens and their aspirations as consumers. It also shows how evolving social attitudes and consumer behaviour create new opportunities for the delivery of publicly acceptable approaches to road pricing. These approaches could also support emerging carbon trading markets. The debate on the acceptability of road pricing has been dominated by the conflict of views between proponents of schemes and opponents of the principle. There is much greater potential for scheme promoters to target delivery at consumers who support road pricing. Incremental growth in road pricing markets can then allow acceptance of road pricing and its delivery to proceed in tandem.
How to design effective road pricing cordons
Authors: Shepherd S. , May A. , Koh A.
Published: July 2008

This paper describes three approaches to cordon location design, a judgemental approach, an optimisation approach based on genetic algorithms and a short-cut approach which lies between the two. The genetic algorithm optimal single cordon generated benefits that were 80% higher than the best judgemental cordon for a simplified network of Edinburgh. The short-cut approach was developed from an observation that charging on only a few of the highest marginal cost links could result in a high proportion of the system optimum or first-best benefits. Initial results for Edinburgh and York have shown that the approach can achieve 93% of the genetic algorithm optimal cordon benefits with only a few model runs in the case of Edinburgh