bluuebunny/crossref_metadata_2025 huggingface dataset:
Iranian Women from Private Sphere to Public Sphere, With Focus on Parliament
Authors: Koolaee Elaheh
Published: February 2010

Women in Iran have gained unprecedented experiences in the course of their fight for democracy and human rights. In the Pahlavi era, the modernisation model was based on Western patterns. With the Islamic Revolution, a new generation of Iranian women emerged in social arenas. Ayatollah Khomeini always emphasised women's prominent and important role in social life. His views shed light on potentials for women's rights, but the obstacle of old cultural and historical attitudes have made these ideas difficult to actualise. The weakness of civil organisations, including women's political and non-political organisations, has seriously affected the outcomes. Although a reformist government and the reinforcement of governmental institutions concerned with women's affairs can play a part in improving the situation of women, women's civil society organisations can assume responsibilities at social levels in order to complement the role of the representatives. The author discusses the process of women's entrance in the public sphere and efforts by the 6th parliament to protect their rights.
Religion as Attachment: The Godin Award Lecture
Authors: Granqvist Pehr
Published: February 2010

In this presentation, I delineate five refinements that I and my associates have introduced during the last decade to the literature on religion and spirituality from an attachment-theory perspective. First, I describe the principle of social correspondence as an addition to the idea that religiousness reflects generalizing working models of attachment. Second, I focus on what we have learned from studying implicit processes and utilizing experimental designs in religion-as-attachment research. Third, I describe results from research projects that have used developmentally validated attachment assessments, such as the Adult Attachment Interview. Fourth, I emphasize the need for engaging a wider developmental range in religion-as-attachment research and sum up what we have found using non-adult samples. Finally, I argue for employing a wider research perspective on the attachment-religion/spirituality connection than the central parameters of an attachment framework would suggest, by considering possible mediators between attachment and religious or spiritual outcomes.
Class, Status, and Party: The Changing Face of Political Islam in Turkey and Egypt
Authors: Gumuscu Sebnem
Published: February 2010

This article argues that socioeconomic changes within Islamist constituencies are critical parts of understanding of how moderate Islamists emerge and succeed. The diverging paths of economic reform in Turkey and Egypt have generated different effects on the Islamist constituencies in these two countries. Economic liberalization has played both a constitutive and a causal role in transformation of political Islam in Turkey by facilitating the growth of a strong devout bourgeoisie with vested interests in liberalism and democracy. With the growing support of this rising devout bourgeoisie, the moderate Islamists managed to transform Islamism into a democratic conservative party. In Egypt, in contrast, the way the state implemented economic reform prevented the formation of as strong and independent a devout bourgeoisie that could be assertive in political Islam. Instead, the lower-middle-class professionals, losers of reform, populated the Islamist constituency and entrenched Islamism in ideological positions rather than pragmatism. This ultimately led to the marginalization of the moderates in Egypt.
A State of Readiness: An Exploration of the Client’s Role in Meeting at Relational Depth
Authors: Knox Rosanne , Cooper Mick
Published: February 2010

It is widely acknowledged that the therapeutic relationship is important to therapeutic outcome. In recent years, there has been additional evidence to suggest that specific, identifiable moments of relational depth between client and therapist can also have a major positive impact on the progress and outcome of therapy; however, the question of how such moments occur remains largely unexplored. Are they solely initiated by the therapist, or does the client have a role too? This article explores clients’ perceptions of the factors facilitating an experience of relational depth. Findings suggest that immediately prior to such an experience the clients themselves have reached a state of readiness, and as making a positive decision to bring their vulnerability to the fore in the therapeutic relationship, thereby facilitating a potential moment of change. Findings are discussed in relation to contemporary theory with implications for practice given.
Experimenting with the Archive: STS-ers As Analysts and Co-constructors of Databases and Other Archival Forms
Authors: Waterton Claire
Published: February 2010

This article is about recent attempts by scholars, database practitioners, and curators to experiment in theoretically interesting ways with the conceptual design and the building of databases, archives, and other information systems. This article uses the term ‘‘archive’’ (following Derrida’s Archive Fever 1998/1995 and Bowker’s Memory Practices in the Sciences 2005) as an overarching category to include a diversity of technologies used to inventory objects and knowledge, to commit them to memory and for future use. The category of ‘‘archive’’ might include forms as diverse as the simple spreadsheet, the species inventory, the computerized database, and the museum. Using this protean concept, this study suggests that we are currently witnessing a time where close convergences are occurring between social theory and archive construction. It identifies a ‘‘move’’ toward exposure of the guts of our archives and databases, toward exposing the contingencies, the framing, the reflexivity, and the politics embedded within them. Within this move, the study examines ways in which theories of performance and emergence have begun to influence the way that archives of different kinds are conceived and reflects on the role of Science and Technology Studies (STS) scholars in their construction.
Case Series
Authors: Treuting Piper M. , Albertson Tina M. , Preston Bradley D.
Published: February 2010

Acute tumor lysis syndrome (ATLS) is characterized by severe metabolic abnormalities and organ dysfunction resulting from rapid destruction of neoplastic cells. Metabolic disturbances are thought to be the primary cause of clinical ATLS symptoms, which include renal dysfunction, seizures, and cardiac arrhythmias. The histopathologic lesions associated with organ dysfunction are largely unknown because of the low rate of mortality of ATLS in humans and the few cases of ATLS identified in laboratory animals. Here, we describe histologic, immunohistochemical, and electron microscopic analyses of thirty-one ATLS cases from a cohort of 499 mice that are prone to spontaneous lymphoblastic lymphoma owing to genetic defects in DNA replication fidelity. Seventy-three percent of our cohort died with lymphoblastic lymphoma, and 8% of affected mice died with diffuse microthromboemboli consistent with ATLS. Mice with ATLS had a high spontaneous mortality rate (>50%), a large tumor burden with disseminated disease, and evidence of leukemia. Blood vessels in the lung, kidney, and other organs were occluded by microthromboemboli composed of chromatin, cellular debris, fibrin, platelets, and entrapped erythrocytes and malignant cells. This case series suggests that ATLS can occur at high frequency in mice with disseminated lymphoblastic lymphoma and leads to a high rate of spontaneous death from microthromboemboli.
The Effects of Targeted Deletion of Cannabinoid Receptors CB1and CB2on Intranasal Sensitization and Challenge with Adjuvant-free Ovalbumin
Authors: Kaplan Barbara L. F. , Lawver Jody E. , Karmaus Peer W. F. , Ngaotepprutaram Thitirat , Birmingham Neil P. , Harkema Jack R. , Kaminski Norbert E.
Published: February 2010

The mechanisms by which cannabinoid receptors CB1and CB2modulate immune function are not fully elucidated. Critical tools for the determination of the role of both receptors in the immune system are CB1/CB2double null mice (CB1/CB2null), and previous studies have shown that CB1/CB2null mice exhibit exaggerated responses to various immunological stimuli. The objective of these studies was to determine the magnitude to which CB1/CB2null mice responded to the respiratory allergen ovalbumin (OVA) as compared with wild-type C57BL/6 mice. The authors determined that in the absence of adjuvant, both wild-type and CB1/CB2null mice mounted a marked response to intranasally instilled OVA as assessed by inflammatory cell infiltrate in the bronchoalveolar lavage fluid (BALF), eosinophilia, induction of mucous cell metaplasia, and IgE production. Many of the endpoints measured in response to OVA were similar in wild-type versus CB1/CB2null mice, with exceptions being modest reductions in OVA-induced IgE and attenuation of BALF neutrophilia in CB1/CB2null mice as compared with wild-type mice. These results suggest that T-cell responses are not universally exaggerated in CB1/CB2null mice.
Short-Term Evaluation of a School-Based Adolescent Injury Prevention Program: Determining Positive Effects or Iatrogenic Outcomes
Authors: Buckley Lisa , Sheehan Mary , Shochet Ian
Published: February 2010

This article reports on the development of a school-based intervention to reduce risk taking and associated injuries. There is limited but important evidence that intervention design should ensure participation does not lead to an increase in target risk behaviors with some studies in alcohol and drug prevention finding unexpected negative effects. The short-term evaluation of Skills for Preventing Injury in Youth (SPIY) examined change in interpersonal violence, alcohol use, and transport-related risks. Intervention ( n = 360) and comparison ( n = 180) students were surveyed pre- and postintervention. A qualitative analysis based on focus groups (70 students) explored experiences of change. Findings indicate significant positive changes reinforced by students’ reports. A decrease in reported risk taking for the intervention group and an increase in the comparison group were observed. These findings endorse SPIY as a useful curriculum approach to reducing injuries and lend support to the future conduct of a long-term outcome evaluation.
Uncertainty and Patient Heterogeneity in Medical Decision Models
Authors: Groot Koerkamp Bas , Weinstein Milton C. , Stijnen Theo , Heijenbrok-Kal M.H. , Hunink M.G. Myriam
Published: February 2010

Parameter uncertainty, patient heterogeneity, and stochastic uncertainty of outcomes are increasingly important concepts in medical decision models. The purpose of this study is to demonstrate the various methods to analyze uncertainty and patient heterogeneity in a decision model. The authors distinguish various purposes of medical decision modeling, serving various stakeholders. Differences and analogies between the analyses are pointed out, as well as practical issues. The analyses are demonstrated with an example comparing imaging tests for patients with chest pain. For complicated analyses step-by-step algorithms are provided. The focus is on Monte Carlo simulation and value of information analysis. Increasing model complexity is a major challenge for probabilistic sensitivity analysis and value of information analysis. The authors discuss nested analyses that are required in patient-level models, and in nonlinear models for analyses of partial value of information analysis.
Time Lost by Driving Fast in the United States
Authors: Redelmeier Donald A. , Bayoumi Ahmed M.
Published: February 2010

Background. Motor vehicle drivers make decisions about speed while traveling and thereby trade off a potential saving from shorter travel time (if the trip is uneventful) against a potential loss of time (if the trip results in a crash). Methods. The authors used computerized modeling based on national data to examine the benefits from small changes in average driver speed on public health in the United States. Lost time due to both travel and crashing was calculated, along with optimal speed to minimize net time lost. Results. The baseline analysis suggested that 1 hour spent driving was associated with approximately 20 minutes of additional lost time in life expectancy due to the potential of a crash. A~1-km/h (0.6-mph) increase in speed for the average driver yielded a~26-second~increase (not decrease) in total expected lost time because the savings from reduced travel time were more than offset by the increased prospect of a crash. A 3.0-km/h (1.8-mph) decrease in average driving speed yielded the least amount of total time lost (95% confidence interval [CI]: 2.5—4.1 km/ h [1.5—2.5 mph]). This speed yielded about 11,000 fewer crashes each day, saved about 3.6 hours per year for the average driver (95% CI: 2.0—6.2 hours), and conserved about 199 cumulative life years for society annually. Conclusions. As a nation, drivers in the United States travel slightly too fast and could improve overall life expectancy by decreasing their average speed slightly.
Children With Autism Spectrum Disorder and Literacy Instruction: An Exploratory Study of Elementary Inclusive Settings
Authors: Whalon Kelly J. , Hart Juliet E.
Published: February 2010

Little is known about how children with autism spectrum disorder (ASD) experience reading instruction in the context of a natural learning environment. This qualitative study centered on three students with ASD who received reading instruction primarily in the general education classroom setting. Observation, interview, and archival data were collected and analyzed to learn how students with ASD engaged in reading instruction and responded to teacher strategies employed to facilitate learning. Findings describe the strengths shown and challenges experienced by children with ASD during literacy instruction. Limited exposure to systematic comprehension instruction hindered the literacy acquisition of learners ASD. Implications for general and special educators are described.
The Effects of Disability-Focused Training on the Attitudes and Perceptions of University Staff
Authors: Murray Christopher , Lombardi Allison , Wren Carol T.
Published: February 2010

This investigation examines the relationship between prior disability-focused training and university staff members’ attitudes toward students with learning disabilities (LD). A survey containing items pertaining to prior disability-focused training experiences and attitudes about students with LD was administered to 300 university staff members. Responses from 112 participants indicated that staff who had not received any form of prior training had greater interest in receiving training regarding LD and had insufficient knowledge to support students with LD. In contrast, staff who had received some form of prior training reported greater scores on general knowledge and sensitivity toward university students with LD. Analyses of training type indicated that staff who had previously participated in disability-related workshops and coursework reported the most positive attitudes, followed by staff who had participated in other forms of training (i.e., reading books and articles or visiting websites). Total number of training types experienced, time spent engaged in training activities, and the amount of time elapsed since training experiences predicted different aspects of staff members’ attitudes and perceptions as well as their satisfaction with prior training. The implications of these findings for future disability-focused professional development efforts within postsecondary settings are discussed.
Examining the Effectiveness of TouchMath With Students With Physical Disabilities
Authors: Avant Mary Jane Thompson , Heller Kathryn Wolff
Published: February 2010

One of the most fundamental math skills for students to learn is basic computational skills. Students who have difficulty learning math skills may benefit from representational approaches, such as TouchMath. A multiprobe, multiple baseline, across-participants design was used in this study to investigate the use of TouchMath with students with physical disabilities. The study was designed to determine the effectiveness of this strategy on the students’ ability to solve basic addition problems with sums to 20. All students were successful in reaching the criterion, with high percentages of correct responses using the TouchMath strategy to answer simple addition problems. Data were analyzed by graphic visual analysis and calculation of the percentage of nonoverlapping data. Generalization and maintenance data supported the effectiveness of this strategy.
A Case Study Comparison of Charter and Traditional Schools in New Orleans Recovery School District
Authors: Wolf Nikki L.
Published: February 2010

In post-Katrina New Orleans, Louisiana, there is a growing concentration of charter schools. The Recovery School District (RSD) has oversight of the majority of these schools. To explore charges from community advocates that RSD charter schools restricted admission and provided inadequate services for students with disabilities, the following questions were asked: Were students with disabilities admitted equally to charter and traditional schools in New Orleans? and How were the services for students with disabilities the same or different in charter and traditional schools? A case study research design that included both traditional and charter RSD schools was used. Data were gathered through examination of relevant reports from school entities and popular media. Additional data were gathered through interviews with district personnel and traditional school, charter school, and community disabilities advocates. Analysis of resultant themes indicated evidence of selective practices as well as differences in education provision for students with disabilities.
Beginning Teacher Challenges Instructing Students Who Are in Foster Care
Authors: Zetlin Andrea , MacLeod Elaine , Kimm Christina
Published: February 2010

Children in foster care compose a population of students very vulnerable to school failure. Placement and school instability and lack of collaboration between the school and child welfare agency are some of the barriers that impede their school performance. This study focused on the classroom context and questioned beginning general and special education teachers in urban schools about their experiences instructing students living in foster care. Findings revealed that foster youth present serious challenges to beginning teachers that go largely unaddressed because of lack of information about the child, lack of teacher preparedness for such challenges, and lack of supports by the school and collaboration with the child welfare system.
Improvement Rate Differences of Academic Interventions for Students With Emotional and Behavioral Disorders
Authors: Vannest Kimberly J. , Harrison Judith R. , Temple-Harvey Kimberly , Ramsey Lunda , Parker Richard I.
Published: February 2010

Academic interventions for students with emotional and behavioral disorders (EBD) is a critical area of practice and one that has not been fully developed by large-scale research. Students with EBD are characterized by an ability to achieve academically but demonstrate a failure to do so. Some research on effective instructional practices for students with EBD does exist, but the predominance of single-case research in this area does not typically demonstrate or report a statistical effect size, making the selection and application of effective instructional strategies sometimes difficult. This article provides a thorough review of the existing research on instructional interventions for students with EBD and calculates effect sizes so that recommending effective instructional practices is more easily accomplished. The authors found 16 “types” of academic interventions and reported the individual and mean improvement rate differences.
Comparing Audio-Supported Text and Explicit Instruction on Students’ Knowledge of Accommodations, Rights, and Responsibilities
Authors: Wood Charles L. , Kelley Kelly R. , Test David W. , Fowler Catherine H.
Published: February 2010

With increasing numbers of students with disabilities entering postsecondary education, it is important to teach students with disabilities their rights and responsibilities governed by civil rights acts (i.e., Section 504 of the Rehabilitation Act of 1973, Americans With Disabilities Act) for requesting accommodations in postsecondary education. This study compared the effects of audio-supported text and explicit instruction on students’ knowledge of their rights, responsibilities, and accommodations in postsecondary education. Participants included four high school seniors with mild disabilities from an urban school district. Using a simultaneous-treatments design with an initial baseline and final best treatment phase, results indicated explicit instruction produced higher scores compared to audio-supported text for all participants. Future research and implications for practice are discussed.
Delay, Doubt, and Decision
Authors: van de Ven Niels , Gilovich Thomas , Zeelenberg Marcel
Published: February 2010

To help explain a regularity in democratic elections, we examined whether choosing to delay making a choice between a focal option and an alternative tends to make people subsequently less likely to choose what they would otherwise have chosen. The results of two experiments demonstrated that participants who were induced to delay making a decision were indeed less likely to choose the descriptively normative option. An additional experiment that primed a sense of doubt in participants provided support for a self-perception account of this result. Electing to delay making a choice is interpreted as an indication of doubt—doubt that tends to be attributed to the most prominent option. Delay-induced doubt about the normative option makes it less likely to be selected.
Context Is Routinely Encoded During Emotion Perception
Authors: Barrett Lisa Feldman , Kensinger Elizabeth A.
Published: February 2010

In the present study, we investigated whether context is routinely encoded during emotion perception. For the first time, we show that people remember the context more often when asked to label an emotion in a facial expression than when asked to judge the expression’s simple affective significance (which can be done on the basis of the structural features of the face alone). Our findings are consistent with an emerging literature showing that facial muscle actions (i.e., structural features of the face), when viewed in isolation, might be insufficient for perceiving emotion.
Unconscious-Thought Effects Take Place Off-Line, Not On-Line
Authors: Strick Madelijn , Dijksterhuis Ap , van Baaren Rick B.
Published: February 2010

The unconscious-thought effect refers to an improvement in decision making following distraction from the decision context for a period of time. The dominant explanation for this effect is that unconscious processes continue to deal with the problem during the distraction period. Recently, however, some researchers have proposed that unconscious thinkers may be merely recalling a judgment that was formed on-line (i.e., during information acquisition). We present two experiments that rule out the latter interpretation. In the unconscious-thought condition of the first experiment, participants who reported making their decision after unconscious thought made better decisions than those who reported making their decision on-line. In the second experiment, all participants judged the choice alternatives both on-line and off-line. On-line judgments were predictive of off-line judgments only in the immediate-decision condition, but not in the conscious- and unconscious-thought conditions. These results demonstrate that a period of unconscious thought does improve judgments that were formed earlier on-line.
Implementation of the Pediatric Early Warning Scoring System on a Pediatric Hematology/Oncology Unit
Authors: Demmel Kathleen M. , Williams Lucinda , Flesch Laura
Published: February 2010

Despite improved outcomes for pediatric Hematology/Oncology patients over the past 15-20 years, sepsis and other acute events continue to cause serious illness in these children. Implementing a pediatric early warning scoring tool (PEWS) with an associated multi-disciplinary action algorithm in a pediatric Hematology/Oncology unit helped to remove barriers that prevented timely referral of children who are clinically deteriorating and requiring immediate help, enhanced multi-disciplinary team communication, and has led to a more than 3-fold increase in days between codes on the Hematology/Oncology unit.
Rural Health: Access to Care and Services
Authors: Nelson Julie A. , Stover Gingerich Barbara
Published: February 2010

Lack of access to quality health care has been a long-standing risk for rural Americans. Multiple factors are emerging that may increase this risk in the future. The National Association for Home Care continuously keeps rural access on the radar and supports legislation that will preserve home care access to vulnerable rural areas. Of special interest are the rural elderly. Rural residents older than the age of 65 years represent a large portion of the nation’s home care recipients. Although people older than 65 years are living longer, healthier lives, they frequently require quality health care to make that possible. This population is also more likely to have complex medical issues requiring health care interventions. A review of current literature shows that there are many emerging trends posing a significant risk to the future of home care in rural America. This article discusses resources as well as initiatives undertaken to identify successful rural care delivery models.
Transitional Case Management: A Method for Establishing Self-Advocacy and Reducing Hospital Readmissions in COPD Patients
Authors: Kilgore Matthew D. C.
Published: February 2010

Patients with chronic obstructive pulmonary disease (COPD) present challenges to the nursing profession. These patients have a high demand for education regarding the management of medications and other aspects of care. A review of the literature shows that a reproducibly effective method for managing these patients outside the hospital setting has not yet been established, and a high percentage of these patients are commonly discharged from the hospital and then quickly readmitted for COPDrelated diagnoses. Good Samaritan Hospital has recently started using a program commonly referred to as transitional case management.This program involves visiting patients initially in the hospital, and then at home, to teach them how to manage their medications, establish a personal health record, and recognize early symptoms of illness so that proper treatment may prevent acute illness. The program is unique in that it assesses a patient’s ability to demonstrate self-management of his or her disease.
Opening Pandora’s Box: A Comprehensive Approach to Home Violence Prevention
Authors: Freysteinson Wyona M.
Published: February 2010

The aim of this article is to describe a comprehensive approach to screening and intervening in home violence. Home care clinicians face a variety of potential abusive situations during the course of home visits. In the home, the victim may be the patient or the caregiver. The offender may be a related, paid, or professional caregiver or the patient. Abuse may be occurring between other persons in the home. A comprehensive home violence program embraces the horizon of abuse possibilities. The practical implications of merging domestic violence and elder abuse paradigms are discussed. Screening of both the patient and the caregiver is encouraged, and interventions are suggested for a number of situations.
The NICU Nutritionist as an Agent of Change
Authors: Goldberg Dena
Published: February 2010

Ensuring that feeding practices are current and evidence based is a fundamental role of the neonatal intensive care unit (NICU) nutritionist. This includes proposing, implementing, and evaluating change in feeding practices when indicated. This article discusses the steps taken to change feeding practices to increase protein intake of very-low-birth-weight infants in a large NICU in a short period of time. The evaluation plan is also discussed.
A Grain of Normality
Authors: Trabi Thomas , Beckenbach Hannes , Ring Stefan , Dunitz-Scheer Marguerite , Scheer Peter J.
Published: February 2010

This case reports highlights of the feeding problems in Marshall-Smith syndrome and the weaning from a tube in a 5-year-old patient. The patient, Maya, showed the typical signs of this rare disease. The diagnosis of Marshall-Smith syndrome was made at the age of 2½ years. Because of respiratory problems and a high risk of aspiration, Maya got a percutaneous endoscopic gastrostomy (PEG) tube at the age of 5 months. After stabilization of her respiratory situation, Maya was able to eat from a strictly medical point of view. Maya was admitted to the authors’ ward dependent on a PEG tube, but her parents wanted her to be weaned from the tube. In contrast to other patients with Marshall-Smith syndrome, Maya’s typical respiratory problems stabilized, and on the basis of the little experience published in the literature, Maya seems to have a relatively good life expectancy. After careful analysis of her medical state, Maya was integrated into the specialized tube-weaning program. Tube weaning was successful, and after 3 weeks of treatment, Maya was able to gain weight by exclusive and self-regulated oral intake. In conclusion, this case report shows that weaning a child with Marshall-Smith syndrome from a feeding tube is possible and gives these children the chance to gain weight by oral intake, as any healthy child does. The reachable eating skills depend on the grade of disability. In the authors’ clinical experience, weaning from a tube shows a positive effect on psychomotor development and reduces the mortality rate and the rate of complications associated with tube feeding itself.
Monocyte activation state regulates monocyte-induced endothelial proliferation through Met signaling
Authors: Schubert Shai Y. , Benarroch Alejandro , Monter-Solans Juan , Edelman Elazer R.
Published: February 2010

Direct interaction of unactivated primary monocytes with endothelial cells induces a mitogenic effect in subconfluent, injured endothelial monolayers through activation of endothelial Met. We now report that monocytes' contact-dependent mitogenicity is controlled by activation-mediated regulation of hepatocyte growth factor. Direct interaction of unactivated monocytes with subconfluent endothelial cells for 12 hours resulted in 9- and 120-fold increase in monocyte tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) mRNA levels and bitemporal spike in hepatocyte growth factor that closely correlates with endothelial Met and extracellular signal-related kinase (ERK) phosphorylation. Once activated, monocytes cannot induce a second wave of endothelial cell proliferation and endothelial Met phosphorylation and soluble hepatocyte growth factor levels fall off. Monocyte-induced proliferation is dose dependent and limited to the induction of a single cell cycle. Monocytes retain their ability to activate other endothelial cells for up to 8 hours after initial interaction, after which they are committed to the specific cell. There is therefore a profoundly sophisticated mode of vascular repair. Confluent endothelial cells ensure vascular quiescence, whereas subconfluence promotes vessel activation. Simultaneously, circulating monocytes stimulate endothelial cell proliferation, but lose this potential once activated. Such a system provides for the fine balance that can restore vascular and endothelial homeostasis with minimal overcompensation.
Signatures of polycomb repression and reduced H3K4 trimethylation are associated with p15INK4b DNA methylation in AML
Authors: Paul Thomas A. , Bies Juraj , Small Donald , Wolff Linda
Published: February 2010

DNA hypermethylation of the p15INK4b tumor suppressor gene is commonly observed in acute myeloid leukemia (AML). Repressive histone modifications and their associated binding proteins have been implicated in the regulation of DNA methylation and the transcriptional repression of genes with DNA methylation. We have used high-density chromatin immunoprecipitation-on-chip to determine the histone modifications that normally regulate p15INK4b expression in AML cells and how these marks are altered in cells that have p15INK4b DNA methylation. In AML patient blasts without p15INK4b DNA methylation, a bivalent pattern of active (H3K4me3) and repressive (H3K27me3) modifications exist at the p15INK4b promoter. AML patient blasts with p15INK4b DNA methylation lose H3K4me3 at p15INK4b and become exclusively marked by H3K27me3. H3K27me3, as well as EZH2, extends throughout p14ARF and p16INK4a, indicating that polycomb repression of p15INK4b is a common feature in all AML blasts irrespective of the DNA methylation status of the gene. Reactivation of p15INK4b expression in AML cell lines and patient blasts using 5-aza-2′-deoxycytidine (decitabine) and trichostatin A increased H3K4me3 and maintained H3K27me3 enrichment at p15INK4b. These data indicate that AML cells with p15INK4b DNA methylation have an altered histone methylation pattern compared with unmethylated samples and that these changes are reversible by epigenetic drugs.
IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Rα in T cells
Authors: Henriques Catarina M. , Rino José , Nibbs Robert J. , Graham Gerry J. , Barata João T.
Published: February 2010

Interleukin-7 (IL-7) is an essential cytokine for T-cell development and homeostasis. It is well established that IL-7 promotes the transcriptional down-regulation of IL7RA, leading to decreased IL-7Rα surface expression. However, it is currently unknown whether IL-7 regulates the intracellular trafficking and early turnover of its receptor on ligand binding. Here, we show that, in steady-state T cells, IL-7Rα is slowly internalized and degraded while a significant fraction recycles back to the surface. On IL-7 stimulation, there is rapid IL-7Rα endocytosis via clathrin-coated pits, decreased receptor recycling, and accelerated lysosome and proteasome-dependent degradation. In accordance, the half-life of IL-7Rα decreases from 24 hours to approximately 3 hours after IL-7 treatment. Interestingly, we further demonstrate that clathrin-dependent endocytosis is necessary for efficient IL-7 signal transduction. In turn, pretreatment of T cells with JAK3 or pan-JAK inhibitors suggests that IL-7Rα degradation depends on the activation of the IL-7 signaling effector JAK3. Overall, our findings indicate that IL-7 triggers rapid IL-7Rα endocytosis, which is required for IL-7–mediated signaling and subsequent receptor degradation.
Clonal expansions of cytotoxic T cells exist in the blood of patients with Waldenström macroglobulinemia but exhibit anergic properties and are eliminated by nucleoside analogue therapy
Authors: Li Jia , Sze Daniel M.-Y. , Brown Ross D. , Cowley Mark J. , Kaplan Warren , Mo Sui-Lin , Yang Shihong , Aklilu Esther , Kabani Karieshma , Loh Yen S. , Yamagishi Tetsuo , Chen Yuling , Ho P. Joy , Joshua Douglas E.
Published: February 2010

T cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+ T-cell receptor Vβ–positive (TCRVβ+)–restricted cytotoxic T-cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report that CTL clones with varying TCRVβ repertoire are present in 70% of patients with Waldenström macroglobulinemia (WM; n = 20). Previous nucleoside analog (NA) therapy, associated with increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRVβ expansions (χ2 = 11.6; P < .001), as 83% of patients without (n = 6) and only 7% with (n = 14) TCRVβ expansions had received NA. Clonality of CD3+CD8+CD57+TCRVβ+-restricted CTLs was confirmed by TCRVβ CDR3 size analysis and direct sequencing. The differential expression of CD3+CD8+CD57+TCRVβ+ cells was profiled using DNA microarrays and validated at mRNA and protein level. By gene set enrichment analysis, CTL clones expressed not only genes from cytotoxic pathways (GZMB, PRF1, FGFBP2) but also genes that suppress apoptosis, inhibit proliferation, arrest cell-cycle G1/S transition, and activate T cells (RAS, CSK, and TOB pathways). Proliferation tracking after stimulation confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity, and nature of clonal CTLs in WM and highlight mechanisms that cause anergy in these cells.
GCS-100, a novel galectin-3 antagonist, modulates MCL-1, NOXA, and cell cycle to induce myeloma cell death
Authors: Streetly Matthew J. , Maharaj Lenushka , Joel Simon , Schey Steve A. , Gribben John G. , Cotter Finbarr E.
Published: February 2010

GCS-100 is a galectin-3 antagonist with an acceptable human safety profile that has been demonstrated to have an antimyeloma effect in the context of bortezomib resistance. In the present study, the mechanisms of action of GCS-100 are elucidated in myeloma cell lines and primary tumor cells. GCS-100 induced inhibition of proliferation, accumulation of cells in sub-G1 and G1 phases, and apoptosis with activation of both caspase-8 and -9 pathways. Dose- and time-dependent decreases in MCL-1 and BCL-XL levels also occurred, accompanied by a rapid induction of NOXA protein, whereas BCL-2, BAX, BAK, BIM, BAD, BID, and PUMA remained unchanged. The cell-cycle inhibitor p21Cip1 was up-regulated by GCS-100, whereas the procycling proteins CYCLIN E2, CYCLIN D2, and CDK6 were all reduced. Reduction in signal transduction was associated with lower levels of activated IκBα, IκB kinase, and AKT as well as lack of IκBα and AKT activation after appropriate cytokine stimulation (insulin-like growth factor-1, tumor necrosis factor-α). Primary myeloma cells showed a direct reduction in proliferation and viability. These data demonstrate that the novel therapeutic molecule, GCS-100, is a potent modifier of myeloma cell biology targeting apoptosis, cell cycle, and intracellular signaling and has potential for myeloma therapy.
Social network types and functional dependency in older adults in Mexico
Authors: Doubova Svetlana Vladislavovna , Pérez-Cuevas Ricardo , Espinosa-Alarcón Patricia , Flores-Hernández Sergio
Published: February 2010

Background

Social networks play a key role in caring for older adults. A better understanding of the characteristics of different social networks types (TSNs) in a given community provides useful information for designing policies to care for this age group. Therefore this study has three objectives: 1) To derive the TSNs among older adults affiliated with the Mexican Institute of Social Security; 2) To describe the main characteristics of the older adults in each TSN, including the instrumental and economic support they receive and their satisfaction with the network; 3) To determine the association between functional dependency and the type of social network.

Methods

Secondary data analysis of the 2006 Survey of Autonomy and Dependency (N = 3,348). The TSNs were identified using the structural approach and cluster analysis. The association between functional dependency and the TSNs was evaluated with Poisson regression with robust variance analysis in which socio-demographic characteristics, lifestyle and medical history covariates were included.

Results

We identified five TSNs: diverse with community participation (12.1%), diverse without community participation (44.3%); widowed (32.0%); nonfriends-restricted (7.6%); nonfamily-restricted (4.0%). Older adults belonging to widowed and restricted networks showed a higher proportion of dependency, negative self-rated health and depression. Older adults with functional dependency more likely belonged to a widowed network (adjusted prevalence ratio 1.5; 95%CI: 1.1-2.1).

Conclusion

The derived TSNs were similar to those described in developed countries. However, we identified the existence of a diverse network without community participation and a widowed network that have not been previously described. These TSNs and restricted networks represent a potential unmet need of social security affiliates.
Consuming cassava as a staple food places children 2-5 years old at risk for inadequate protein intake, an observational study in Kenya and Nigeria
Authors: Stephenson Kevin , Amthor Rachel , Mallowa Sally , Nungo Rhoda , Maziya-Dixon Busie , Gichuki Simon , Mbanaso Ada , Manary Mark
Published: February 2010

Background

Inadequate protein intake is known to be deleterious in animals. Using WHO consensus documents for human nutrient requirements, the protein:energy ratio (P:E) of an adequate diet is > 5%. Cassava has a very low protein content. This study tested the hypothesis that Nigerian and Kenyan children consuming cassava as their staple food are at greater risk for inadequate dietary protein intake than those children who consume less cassava.

Methods

A 24 hour dietary recall was used to determine the food and nutrient intake of 656 Nigerian and 449 Kenyan children aged 2-5 years residing in areas where cassava is a staple food. Anthropometric measurements were conducted. Diets were scored for diversity using a 12 point score. Pearson's Correlation Coefficients were calculated to relate the fraction of dietary energy obtained from cassava with protein intake, P:E, and dietary diversity.

Results

The fraction of dietary energy obtained from cassava was > 25% in 35% of Nigerian children and 89% of Kenyan children. The mean dietary diversity score was 4.0 in Nigerian children and 4.5 in Kenyan children, although the mean number of different foods consumed on the survey day in Nigeria was greater than Kenya, 7.0 compared to 4.6. 13% of Nigerian and 53% of Kenyan children surveyed had inadequate protein intake. The fraction of dietary energy derived from cassava was negatively correlated with protein intake, P:E, and dietary diversity. Height-for age z score was directly associated with protein intake and negatively associated with cassava consumption using regression modeling that controlled for energy and zinc intake.

Conclusions

Inadequate protein intake was found in the diets of Nigerian and Kenyan children consuming cassava as a staple food. Inadequate dietary protein intake is associated with stunting in this population. Interventions to increase protein intake in this vulnerable population should be the focus of future work.
Hypofractionated radiotherapy for lung tumors with online cone beam CT guidance and active breathing control
Authors: Shen Yali , Zhang Hong , Wang Jin , Zhong Renming , Jiang Xiaoqing , Xu Qinfeng , Wang Xin , Bai Sen , Xu Feng
Published: February 2010

Background

To study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT) guided hypofractionated radiotherapy with active breathing control (ABC) for patients with non-small cell lung cancer (NSCLC) or metastatic tumors in lung.

Methods

32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed.

Results

The pre-correction systematic and random errors in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20%) grade1-2 acute pneumonitis, 3 (15%) grade1 acute esophagitis, 2 (10%) grade1 late pneumonitis and 1 (5%) grade 1 late esophagitis.

Conclusion

The positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used.
A modular positive feedback-based gene amplifier
Authors: Nistala Goutam J , Wu Kang , Rao Christopher V , Bhalerao Kaustubh D
Published: February 2010

Background

Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors.

Results

We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity.

Conclusions

The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.
Family-related adverse childhood experiences as risk factors for
psychiatric disorders in Nigeria
Authors: Oladeji Bibilola D. , Makanjuola Victor A. , Gureje Oye
Published: March 2010

Background

Adverse childhood experiences have been associated with a variety of
mental health problems in adult life.

Aims

To examine whether this reported link between childhood experiences and
mental health disorders in adult life applies in a Sub-Saharan African
setting where cultural and family attributes may be different.

Method

A multistage random sampling was used in the Nigerian Survey of Mental
Health and Well-Being (NSMHW) to select respondents for face-to-face
interviews. Assessments of family-related adverse childhood experiences
and lifetime mental health disorders were conducted with the Composite
International Diagnostic Interview (CIDI 3.0).

Results

Almost half of the respondents had experienced an adverse childhood
experience within the context of the family before they were 16 years of
age. Associations between adverse childhood experiences and adult mental
health disorders were few and were attenuated when clustering of adverse
childhood experience and disorder comorbidities were accounted for. There
was an elevated likelihood of adult substance use disorders among
individuals who had experienced family violence and neglect or abuse.
Parental psychopathology was associated with a significantly increased
risk for developing mood disorders.

Conclusions

Adverse childhood experiences reflecting violence in the family, parental
criminality and parental mental illness and substance misuse were more
likely to have significant mental health consequences in adulthood.