bluuebunny/crossref_metadata_2025 huggingface dataset:
Disaster Policies
Authors: Wildasin David E.
Published: June 2008

Although major disasters like the 2005 Gulf Coast hurricanes are infrequent, they dominate empirical loss distributions, as illustrated by a statistical analysis of flood losses in Louisiana. Extraordinary Federal emergency assistance has shifted a large portion of the burden of the 2005 floods to the rest of society, relieving financial stress in the disaster-stricken region but raising serious questions about the incentives for subnational governments to implement costly but efficient disaster avoidance policies in the future. The Federal government cannot credibly commit not to insure losses from future disasters, nor can it efficiently assume responsibility for land use, economic development, and other state and local government policies that affect disaster risk. Mandatory disaster reserves provide an alternative policy option through which actuarially fair Federal insurance could credibly strengthen the incentives for efficient subnational government disaster policies.
The Effects of Changes in Michigan's School Finance System
Authors: Papke Leslie E.
Published: June 2008

I use district-level panel data from the 1991/92 school year through the 2003/04 school year to study the effects of Proposal A, passed in Michigan in 1994. Proposal A dramatically changed the way schools were funded starting in the 1994/95 school year. I discuss what has happened to the pattern of spending in years before and after the reform, including a discussion of funding equalization. Using the several additional years of data—which include additional periods of substantial funding increases for low-spending districts—and a richer lag structure in an econometric model, I find that increases in spending have nontrivial, statistically significant effects on math test pass rates. The effects are notably larger for districts with initially poor performance.
Connecting for Health Literacy: Health Information Partners
Authors: Pomerantz Karyn L. , Muhammad Abdul-Ali , Downey Stacey , Kind Terry
Published: June 2008

This article describes a community-based health information partnership to address health literacy and health information inequalities in marginalized communities. Public health, medical, literacy, and library practitioners promote health literacy through outreach, training, and professional development activities in community settings. They create learning environments for people to develop the necessary knowledge and skills to better understand health information and health policy so they can make decisions concerning personal and community health. Outreach activities focus on visits to neighborhood health centers, health fairs, health exhibits at union meetings and conferences; training programs involve hands-on, peer-led computer classes for people living with HIV and for the general public; and professional development programs connect librarians, health providers, public health workers, and literacy teachers in joint planning and learning. Several learners currently participate in and lead community health education programs and HIV advocacy. The coalition’s strength develops from strongly shared objectives, an absence of territoriality, and a core active leadership group.
Safe in the City: Developing an Effective Video-Based Intervention for STD Clinic Waiting Rooms
Authors: Myint-U Athi , Bull Sheana , Greenwood Gregory L. , Patterson Jocelyn , Rietmeijer Cornelis A. , Vrungos Shelley , Warner Lee , Moss Jesse , O'Donnell Lydia N.
Published: June 2008

There is a strong need for inexpensive, easily administered HIV and STD prevention interventions that are highly replicable and appealing to diverse clinic audiences. This article describes the four-step iterative and collaborative process used by the Safe City Study Group to design and develop a brief video-based intervention: Safe in the City. Step 1 involves identification of an appropriate intervention medium, a theoretical framework, and key messages; Step 2, collaboration with a film company to integrate the framework and key messages into an entertaining product; Step 3, facilitation of a multistep participatory process involving input from members of the priority audience (clinic patients), clinic staff, and community reviewers; and Step 4, pilot-testing to determine structural barriers to patients’ viewing the video in clinic waiting rooms. Safe in the City has been demonstrated to reduce incident STDs among clinic patients in three cities in the United States.
The North Carolina Evidence-Based Transition-to-Practice Initiative
Authors: Wolf Roth Joyce
Published: June 2008

Successful transition of newly licensed nurses into practice is essential for safe nursing practice. North Carolina has begun an initiative to implement an evidence-based formal transition-to-practice requirement for all newly licensed entry-level nurses in the state by 2015. Phase I of this collaborative project uses a longitudinal design to study new nurse—preceptor dyads. Resulting data will describe competence and confidence development in newly licensed North Carolina RNs practicing in acute care hospitals. Longitudinal data about practice errors and risk for practice breakdown in the first 6 months of the newly licensed nurse's employment will also be collected. The study will provide data to determine the essential components of this evidence-based transition requirement and will contribute to the evidence base for best practices related to transition experiences for newly licensed RNs.
A Curricular-Sampling Approach to Progress Monitoring
Authors: Fuchs Lynn S. , Fuchs Douglas , Zumeta Rebecca O.
Published: June 2008

Progress monitoring is an important component of effective instructional practice. Curriculum-based measurement (CBM) is a form of progress monitoring that has been the focus of rigorous research. Two approaches for formulating CBM systems exist. The first is to assess performance regularly on a task that serves as a global indicator of competence at the relevant grade level. The second approach is to systematically sample the year-long curriculum so that each skill is represented and receives the same emphasis on each alternate form. In this article, the systematic curriculum sampling approach is illustrated for monitoring progress in mathematics concepts and applications systems. A description of the system's components, background, and technical properties is provided. Then, a sample case explains how the CBM system can be used in a special education setting to monitor progress, plan instruction, and enhance communication.
Tumor Versus Tumor-Associated Macrophages: How Hot is the Link?
Authors: Guruvayoorappan C.
Published: June 2008

One of the functions of macrophages is to provide a defense mechanism against tumor cells. In contrast, tumor-associated macrophages (TAMs), which represent the major inflammatory component of the stroma of many tumors, are associated with tumor progression and metastasis. TAMs, in contrast with normal macrophages, exhibit the M2 phenotype, and thereby exhibit pro-tumoral functions, including angiogenesis and matrix remodeling. This review will discuss the role of TAMs in tumor progression and provide an overview of their significant part in tumor metastasis and angiogenesis.
The Tumoricidal Effect of Sonodynamic Therapy (SDT) on S-180 Sarcoma in Mice
Authors: Xiaohuai Wang  , Lewis Thomas J. , Mitchell Doug
Published: June 2008

There are increasing data showing that sonodynamic therapy (SDT), which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. However, few clinical data on SDT have been published. One reason is the lack of suitable drugs for clinical SDT use. Recently a new sonosensitizing agent has been developed by SonneMed, LLC, referred to as SF1. In this study the effect of SDT with SF1 on S-180 sarcoma in mice was examined. The tumor bearing mice were allocated to the following groups: (1) sham-treatment (control, C); (2) ultrasound treatment (only ultrasound treatment, 1.2 mW/cm2 , without SF1, U); (3) SF1 treatment (SF1 20 mg/kg intraperitoneal [ip] without ultrasound treatment, S); and (4) SF1 + ultrasound treatment (SU). Following treatment, tumor volume was monitored. Tumor growth inhibition was seen only in group SU, and with increasing ultrasound intensity, the inhibitory effect was enhanced. Tumor growth inhibition was also visible even when covered by a barrier of bone. Pathological slices showed coagulated necrosis or metamorphic tissue with inflammatory reaction in the tumor taken from 2 to 36 hours after SDT. These data revealed that SDT with SF1 did inhibit growth of mouse S-180 sarcoma and the inhibitory effect was sound intensity dependent. SDT also induced some inflammation while it destroyed the tumor, indicative of a “vaccine” effect. SF1 shows great promise for clinical use in the future.
Facing the Challenges of Hematopoietic Stem Cell Transplantation With Mindfulness Meditation: A Pilot Study
Authors: Bauer-Wu Susan , Sullivan Amy M. , Rosenbaum Elana , Ott Mary Jane , Powell Mark , McLoughlin Margo , Healey Martha W.
Published: June 2008

The hematopoietic stem cell transplant (HSCT) experience is emotionally and physically stressful for cancer patients who undergo this procedure. Mindfulness-based interventions have been studied in patients with various diagnoses, including cancer, although minimal work has applied this intervention to hospitalized patients. Use of mindfulness meditation has potential to provide HSCT patients with coping skills to deal with unpleasant symptoms and an uncertain future. This exploratory study examined feasibility, physiological arousal, and psychological and physical symptoms in HSCT patients participating in a mindfulness meditation intervention that begins before and continues throughout hospitalization and involves one-on-one guided sessions and daily practice using a 17-minute meditation CD. Of the 20 participants, 78.9% completed the intervention. Statistically significant decreases in heart and respiratory rates and improvements in symptoms immediately before and after each session were found. These findings demonstrate feasibility and preliminary support of a mindfulness meditation intervention with symptomatic, hospitalized cancer patients.
Toll-like receptor–mediated activation of neutrophils by influenza A virus
Authors: Wang Jennifer P. , Bowen Glennice N. , Padden Carolyn , Cerny Anna , Finberg Robert W. , Newburger Peter E. , Kurt-Jones Evelyn A.
Published: June 2008

Influenza virus infection of the respiratory tract is characterized by a neutrophil infiltrate accompanied by inflammatory cytokine and chemokine production. We and others have reported that Toll-like receptor (TLR) proteins are present on human neutrophils and that granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment enhances IL-8 (CXCL8) secretion in response to stimulation with TLR ligands. We demonstrate that influenza virus can induce IL-8 and other inflammatory cytokines from GM-CSF–primed human neutrophils. Using heat inactivation of influenza virus, we show that viral entry but not replication is required for cytokine induction. Furthermore, endosomal acidification and viral uncoating are necessary. Finally, using single-cell analysis of intracellular cytokine accumulation in neutrophils from knockout mice, we prove that TLR7 is essential for influenza viral recognition and inflammatory cytokine production by murine neutrophils. These studies demonstrate neutrophil activation by influenza virus and highlight the importance of TLR7 and TLR8 in that response.
mTOR inhibitors are synergistic with methotrexate: an effective combination to treat acute lymphoblastic leukemia
Authors: Teachey David T. , Sheen Cecilia , Hall Junior , Ryan Theresa , Brown Valerie I. , Fish Jonathan , Reid Gregor S. D. , Seif Alix E. , Norris Robin , Chang Yueh J. , Carroll Martin , Grupp Stephan A.
Published: June 2008

We have previously demonstrated that mTOR inhibitors (MTIs) are active in preclinical models of acute lymphoblastic leukemia (ALL). MTIs may increase degradation of cyclin D1, a protein involved in dihydrofolate reductase (DHFR) synthesis. Because resistance to methotrexate may correlate with high DHFR expression, we hypothesized MTIs may increase sensitivity of ALL to methotrexate through decreasing DHFR by increasing turn-over of cyclin D1. We tested this hypothesis using multiple ALL cell lines and nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenografted with human ALL. We found MTIs and methotrexate were synergistic in combination in vitro and in vivo. Mice treated with both drugs went into a complete and durable remission whereas single agent treatment caused an initial partial response that ultimately progressed. ALL cells treated with MTIs had markedly decreased expression of DHFR and cyclin D1, providing a novel mechanistic explanation for a combined effect. We found methotrexate and MTIs are an effective and potentially synergistic combination in ALL.
CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin αIIbβ3 in platelets
Authors: Cifuni Stephen M. , Wagner Denisa D. , Bergmeier Wolfgang
Published: June 2008

Second messenger-mediated inside-out activation of integrin αIIbβ3 is a key step in platelet aggregation. We recently showed strongly impaired but not absent αIIbβ3-mediated aggregation of CalDAG-GEFI–deficient platelets activated with various agonists. Here we further evaluated the roles of CalDAG-GEFI and protein kinase C (PKC) for αIIbβ3 activation in platelets activated with a PAR4 receptor–specific agonist, GYPGKF (PAR4p). Compared with wild-type controls, platelets treated with the PKC inhibitor Ro31-8220 or CalDAG-GEFI–deficient platelets showed a marked defect in aggregation at low (< 1mM PAR4p) but not high PAR4p concentrations. Blocking of PKC function in CalDAG-GEFI–deficient platelets, how-ever, strongly decreased aggregation at all PAR4p concentrations, demonstrating that CalDAG-GEFI and PKC represent separate, but synergizing, pathways important for αIIbβ3 activation. PAR4p-induced aggregation in the absence of CalDAG-GEFI required cosignaling through the Gαi-coupled receptor for ADP, P2Y12. Independent roles for CalDAG-GEFI and PKC/Gαi signaling were also observed for PAR4p-induced activation of the small GTPase Rap1, with CalDAG-GEFI mediating the rapid but reversible activation of this small GTPase. In summary, our study identifies CalDAG-GEFI and PKC as independent pathways leading to Rap1 and αIIbβ3 activation in mouse platelets activated through the PAR4 receptor.
Polyphosphate enhances fibrin clot structure
Authors: Smith Stephanie A. , Morrissey James H.
Published: June 2008

Polyphosphate, a linear polymer of inorganic phosphate, is present in platelet dense granules and is secreted on platelet activation. We recently reported that polyphosphate is a potent hemostatic regulator, serving to activate the contact pathway of blood clotting and accelerate factor V activation. Because polyphosphate did not alter thrombin clotting times, it appeared to exert all its procoagulant actions upstream of thrombin. We now report that polyphosphate enhances fibrin clot structure in a calcium-dependent manner. Fibrin clots formed in the presence of polyphosphate had up to 3-fold higher turbidity, had higher mass-length ratios, and exhibited thicker fibers in scanning electron micrographs. The ability of polyphosphate to enhance fibrin clot turbidity was independent of factor XIIIa activity. When plasmin or a combination of plasminogen and tissue plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of polyphosphate exhibited prolonged clot lysis times. Release of polyphosphate from activated platelets or infectious microorganisms may play an important role in modulating fibrin clot structure and increasing its resistance to fibrinolysis. Polyphosphate may also be useful in enhancing the structure of surgical fibrin sealants.
FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2−/−γC−/− mice in vivo
Authors: Jiang Qi , Zhang Liguo , Wang Rui , Jeffrey Jerry , Washburn Michael L. , Brouwer Dedeke , Barbour Selena , Kovalev Grigoriy I. , Unutmaz Derya , Su Lishan
Published: June 2008

The role of FoxP3+CD4+ regulatory T (Treg) cells in HIV-1 disease in vivo is poorly understood due to the lack of a robust model. We report here that CD4+FoxP3+ T cells are developed in all lymphoid organs in humanized Rag2−/−γC−/− (DKO-hu HSC) mice and they display both Treg phenotype and Treg function. These FoxP3+ Treg cells are preferentially infected and depleted by a pathogenic HIV-1 isolate in HIV-infected DKO-hu HSC mice; and depletion of Treg cells is correlated with induction of their apoptosis in vivo. When CD4+CD25+/hi Treg cells are depleted with the IL-2–toxin fusion protein (denileukin diftitox), HIV-1 infection is significantly impaired. This is demonstrated by reduced levels of productively infected cells in lymphoid organs and lower plasma viremia. Therefore, FoxP3+ Treg cells are productively infected and play an important role in acute HIV-1 infection in vivo. The DKO-hu HSC mouse will be a valuable model to study human Treg functions and their role in HIV-1 pathogenesis in vivo.
Knowledge, attitudes, and preventive practices about colorectal cancer among adults in an area of Southern Italy
Authors: Sessa Alessandra , Abbate Rossella , Di Giuseppe Gabriella , Marinelli Paolo , Angelillo Italo F
Published: June 2008

Background

Colorectal cancer (CRC) is the second most commonly diagnosed cancer for both sexes in developed countries. This study assessed the knowledge, attitudes, and preventive practices regarding CRC of adults in Italy.

Methods

A random sample of 1165 adults received a self-administered questionnaire on socio-demographic characteristics; knowledge regarding definition, risk factors, and screening; attitudes regarding perceived risk of contracting CRC and utility of screening tests; health-related behaviors and health care use; source of information.

Results

Only 18.5% knew the two main modifiable risk factors (low physical activity, high caloric intake from fat) and this knowledge was significantly associated with higher educational level, performing physical activity, modification of dietary habits and physical activity for fear of contracting CRC, and lower risk perception of contracting CRC. Half of respondents identified fecal occult blood testing (FOBT) as main test for CRC prevention and were more knowledgeable those unmarried, more educated, who knew the main risk factors of CRC, and have received advice by physician of performing FOBT. Personal opinion that screening is useful for CRC prevention was high with a mean score of 8.3 and it was predicted by respondents' lower education, beliefs that CRC can be prevented, higher personal perceived risk of contracting CRC, and information received by physician about CRC. An appropriate behavior of performing FOBT if eligible or not performing if not eligible was significantly higher in female, younger, more educated, in those who have been recommended by physician for undergo or not undergo FOBT, and who have not personal history of precancerous lesions and familial history of precancerous lesions or CRC.

Conclusion

Linkages between health care and educational systems are needed to improve the levels of knowledge and to raise CRC screening adherence.
Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary
Authors: Sharov Alexei A , Falco Geppino , Piao Yulan , Poosala Suresh , Becker Kevin G , Zonderman Alan B , Longo Dan L , Schlessinger David , Ko Minoru SH
Published: June 2008

Background

The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice onad libitum(AL) feeding with a group on lifespan-extending 40% calorie restriction (CR).

Results

We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis.

Conclusion

Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.
Pre-clinical development as microbicide of zinc tetra-ascorbo-camphorate, a novel terpenoid derivative: Potent in vitro inhibitory activity against both R5- and X4-tropic HIV-1 strains without significant in vivo mucosal toxicity
Authors: Saïdi Héla , Jenabian Mohammad-Ali , Gombert Bernard , Charpentier Charlotte , Mannarini Aurèle , Bélec Laurent
Published: June 2008

Background

Terpenoid derivatives originating from many plants species, are interesting compounds with numerous biological effects, such as anti-HIV-1 activity. The zinc tetra-ascorbo-camphorate complex (or "C14"), a new monoterpenoid derivative was evaluated in vitro for its anti-HIV-1 activity on both R5- and X4-HIV-1 infection of primary target cells (macrophages, dendritic cells and T cells) and on HIV-1 transfer from dendritic cells to T cells.

Results

The toxicity study was carried out in vitro and also with the New Zealand White rabbit vaginal irritation model. C14 was found to be no cytotoxic at high concentrations (CC50 > 10 μM) and showed to be a potential HIV-1 inhibitor of infection of all the primary cells tested (EC50 = 1 μM). No significant changes could be observed in cervicovaginal tissue of rabbit exposed during 10 consecutive days to formulations containing up to 20 μM of C14.

Conclusion

Overall, these preclinical studies suggest that zinc tetra-ascorbo-camphorate derivative is suitable for further testing as a candidate microbicide to prevent male-to-female heterosexual acquisition of HIV-1.
The occurrence of osteoarthritis at a minimum of ten years after reconstruction of the anterior cruciate ligament
Authors: van der Hart Cor P , van den Bekerom Michel PJ , Patt Thomas W
Published: June 2008

Objective

The objective of this study was to evaluate the incidence of radiographic osteoarthritis in the operated knee in comparison with the contralateral knee ten years after a bone-tendon bone patellar autograft ACL-reconstruction and to evaluate to which level patients regain activity ten years after reconstruction.

Methods

Fifty-three patients with ACL instability were operated arthroscopically using the central third of the patellar tendon as a bone-tendon-bone autograft. At a minimum of 10 year follow up 28/44 patients matched the inclusion criteria and could be reached for follow-up. Evaluation included a patient satisfaction evaluation using a Visual Analog Scale, physical examination (International Knee Documentation Committee score, Tegner score, Lysholm score, KT-1000 stabilometry) and a radiological evaluation (Kellgren and Fairbanks classification).

Results

The patients' satisfaction, at a mean of 10,3 year follow-up, measured with a VAS score (0–10) was high with a mean of 8.5 (range 4 to 10). The KT 1000 arthrometer laxity measurements revealed in 55% of the patients an A rating (1–2 mm), in 29% a B rating (3–5 mm) and in 16% a C rating (6–10 mm). According to the Tegner score 54% of the patients were able to perform at the same activity level as pre-operatively. The mean pre-operative Tegner score was 6.8 and the mean post-operative Tegner score was 6.0 at final follow up. The Lysholm score showed satisfactory results with a mean of 91 points (range 56 to 100). According to the Kellgren and Fairbank classifications, there is a significant difference (p < 0.05) in development of OA between the ACL injured and subsequently operated knee in comparison to the contralateral knee.

Conclusion

The patellar BTB ACL reconstruction does not prevent the occurrence of radiological OA after 10 years but does help the patient to regain the pre-operative level of activity.
Decrease in tobacco consumption after treatment with topiramate and aripiprazole: a case report
Authors: Arbaizar Beatriz , Gómez-Acebo Inés , Llorca Javier
Published: June 2008

Introduction

A large part of research into drug addiction focuses on mesolimbic dopamine circuitry; however, both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and/or kainate and dopamine D2 receptors can play a role in maintaining the established addiction.

Case presentation

We report the case of a 34-year-old man who compulsively smoked 80 to 100 cigarettes each day. After receiving treatment with topiramate and aripiprazole, his tobacco consumption was dramatically reduced.

Conclusion

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and/or kainate blocking agents and a dopamine D2 receptor partial agonist may be novel instruments for nicotine abuse disorders.
Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis
Authors: Scales Damon C , Thiruchelvam Deva , Kiss Alexander , Sibbald William J , Redelmeier Donald A
Published: June 2008

Introduction

Intensive care unit (ICU) admission for bone marrow transplant recipients immediately following transplantation is an ominous event, yet the survival of these patients with subsequent ICU admissions is unknown. Our objective was to determine the long-term outcome of bone marrow transplant recipients admitted to an ICU during subsequent hospitalizations.

Methods

We conducted a population-based cohort analysis of all adult bone marrow transplant recipients who received subsequent ICU care in Ontario, Canada from 1 January 1992 to 31 March 2002. The primary endpoint was mortality at 1 year.

Results

A total of 2,653 patients received bone marrow transplantation; 504 of which received ICU care during a subsequent hospitalization. Patients receiving any major procedure during their ICU stay had higher 1-year mortality than those patients who received no ICU procedure (87% versus 44%, P < 0.0001). Death rates at 1 year were highest for those receiving mechanical ventilation (87%), pulmonary artery catheterization (91%), or hemodialysis (94%). In combination, the strongest independent predictors of death at 1 year were mechanical ventilation (odds ratio, 7.4; 95% confidence interval, 4.8 to 11.4) and hemodialysis (odds ratio, 8.7; 95% confidence interval, 2.1 to 36.7), yet no combination of procedures uniformly predicted 100% mortality.

Conclusion

The prognosis of bone marrow transplant recipients receiving ICU care during subsequent hospitalizations is very poor but should not be considered futile.
Bone Metabolism in Adolescent Boys with Anorexia Nervosa
Authors: Misra Madhusmita , Katzman Debra K. , Cord Jennalee , Manning Stephanie J. , Mendes Nara , Herzog David B. , Miller Karen K. , Klibanski Anne
Published: June 2008

Background: Anorexia nervosa (AN) is a condition of severe undernutrition associated with low bone mineral density (BMD) in adolescent females with this disorder. Although primarily a disease in females, AN is increasingly being recognized in males. However, there are few or no data regarding BMD, bone turnover markers or their predictors in adolescent AN boys.

Hypotheses: We hypothesized that BMD would be low in adolescent boys with AN compared with controls associated with a decrease in bone turnover markers, and that the gonadal steroids, testosterone and estradiol, and levels of IGF-I and the appetite regulatory hormones leptin, ghrelin, and peptide YY would predict BMD and bone turnover markers.

Methods: We assessed BMD using dual-energy x-ray absorptiometry and measured fasting testosterone, estradiol, IGF-I, leptin, ghrelin, and peptide YY and a bone formation (aminoterminal propeptide of type 1 procollagen) and bone resorption (N-telopeptide of type 1 collagen) marker in 17 AN boys and 17 controls 12–19 yr old.

Results: Boys with AN had lower BMD and corresponding Z-scores at the spine, hip, femoral neck, trochanter, intertrochanteric region, and whole body, compared with controls. Height-adjusted measures (lumbar bone mineral apparent density and whole body bone mineral content/height) were also lower. Bone formation and resorption markers were reduced in AN, indicating decreased bone turnover. Testosterone and lean mass predicted BMD. IGF-I was an important predictor of bone turnover markers.

Conclusion: AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass.
Comparison of Daily, Weekly, and Monthly Vitamin D3 in Ethanol Dosing Protocols for Two Months in Elderly Hip Fracture Patients
Authors: Ish-Shalom Sophia , Segal Elena , Salganik Tina , Raz Batia , Bromberg Irvin L. , Vieth Reinhold
Published: June 2008

Background: Different dosing protocols have been used for vitamin D supplementation, but there has been a lack of comparative data among them.

Objective: Our objective was to determine whether the same cumulative dose of vitamin D3 produces different effects if it is given daily, weekly, or monthly.

Design: Women, age 81 ± 8 yr (± sd, n = 48), who had undergone surgery to repair hip fracture were randomized to vitamin D3-supplementation protocols at 1,500 IU daily, or 10,500 IU once weekly, or 45,000 IU once every 28 d. The primary outcome measure was the serum 25-hydroxyvitamin D [25(OH)D] concentration attained.

Results: Initially, serum 25(OH)D concentrations for daily, weekly, and monthly groups were, respectively, 15.13 ± 6.9, 15.7 ± 10.1, and 16.2 ± 10.1 ng/ml. By d 7, these had increased significantly in all the groups (P < 0.001). On the first day after the monthly dose, both serum 25(OH)D and serum 1,25-dihydroxyvitamin D had increased significantly (P < 0.012 each), whereas these did not change significantly on the day after daily or weekly doses. After 2 months, serum 25(OH)D with daily, weekly, and monthly dosing were, respectively, 33.2 ± 8.5, 29.2 ± 8.9, and 37.1 ± 10.3 ng/ml; there were no significant differences among these values.

Conclusions: Supplementation with vitamin D can be achieved equally well with daily, weekly, or monthly dosing frequencies. Therefore, the choice of dose frequency can be based on whichever approach will optimize an individual’s adherence with long-term vitamin D supplementation.
Growth-Promoting Effect of Rh(D) Antibody on Human Pancreatic Islet Cells
Authors: Feller John M. , Simpson Ann M. , Nelson Margaret , Swan M. Anne , O'Connell Philip J. , Hawthorne Wayne J. , Tao Chang , O'Brien Bronwyn A.
Published: June 2008

Context/Objective: Hyperinsulinism with islet cell hyperplasia is a frequent complication, of unknown cause, in hemolytic disease of the newborn, occurring in Rh(D)-positive infants of Rh-isoimmunized Rh(D)-negative mothers, but not in infants with other hemolytic disorders. We investigated the possibility that trans-placentally acquired anti-D Ig is the cause of both conditions.

Design: Monolayer cultures of human islet cells were exposed to sera from Rh-isoimmunized mothers and newborns, where jaundice, hyperinsulinism, and hypoglycemia in the infant had ensued. Parallel cultures with anti-D, specific anti-D monoclonal antibodies, normal human Ig (15 μg/ml), and serum controls were also undertaken. Islet cell proliferation was determined by [3H]thymidine incorporation. Insulin storage and chronic and acute insulin secretion to glucose were analyzed by RIA. Rh(D) surface antigen expression was determined on islet cells by flow cytometric analysis.

Results: Islet cell proliferation and insulin secretion were significantly greater in coculture with test sera (P < 0.01; n = 8) and with anti-D (P < 0.001; n = 8), compared with either controls or Ig. After 8 d of growth, the static incubation experiment showed a 3.5-fold response to glucose stimulus in all sera. Rh(D) antigen expression was detected on the islet cell surface by flow cytometry, and islet cell morphology was normal. Colocalization of the proliferation marker Ki67 with insulin by immunofluorescent staining further indicated that Rh(D) antibody promoted islet growth.

Conclusions: The anti-Rh(D) islet cell proliferative effect generates neonatal hyperinsulinism in Rh isoimmunization. Anti-Rh(D) may have application for islet cell proliferation in diabetes mellitus treatment for Rh(D)-positive subjects. Further analysis is required.
Interaction of Mint3 with Furin regulates the localization of Furin in the trans-Golgi network
Authors: Han Jinbo , Wang Yiguo , Wang Suming , Chi Chengwu
Published: June 2008

Furin is a proprotein convertase that cycles between the plasma membrane, endosomes and the trans-Golgi network (TGN), maintaining a predominant distribution in the latter. Mint3, a member of the Mint protein family, is involved in the signaling and trafficking of membrane proteins. Until now, little has been known about the roles of Mint3 in the localization or trafficking of Furin. Here, using co-immunoprecipitation and immunofluorescence assays, we show that Mint3 interacts with Furin in the Golgi compartment of HeLa cells. Knockdown of endogenous Mint3 expression by RNA interference disrupts the TGN-specific localization of Furin and increases its distribution in endosomes. We further demonstrate that the phosphotyrosine-binding (PTB) domain of Mint3 is essential for the binding of Furin and that this binding affects the TGN-specific localization of Furin. Moreover, mutation studies of Furin indicate that Mint3 regulates Furin distribution mainly through interaction with the acidic peptide signal of Furin. Collectively, these data suggest that the interaction between the PTB domain of Mint3 and the acidic peptide signal of Furin regulates the specific localization of Furin in the TGN.
Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2
Authors: Murphy Jane E. , Vohra Ravinder S. , Dunn Sarah , Holloway Zoe G. , Monaco Anthony P. , Homer-Vanniasinkam Shervanthi , Walker John H. , Ponnambalam Sreenivasan
Published: June 2008

The LOX-1 scavenger receptor recognises pro-atherogenic oxidised low-density lipoprotein (OxLDL) particles and is implicated in atherosclerotic plaque formation, but this mechanism is not well understood. Here we show evidence for a novel clathrin-independent and cytosolic-signal-dependent pathway that regulates LOX-1-mediated OxLDL internalisation. Cell surface labelling in the absence or presence of OxLDL ligand showed that LOX-1 is constitutively internalised from the plasma membrane and its half-life is not altered upon ligand binding and trafficking. We show that LOX-1-mediated OxLDL uptake is disrupted by overexpression of dominant-negative dynamin-2 but unaffected by CHC17 or μ2 (AP2) depletion. Site-directed mutagenesis revealed a conserved and novel cytoplasmic tripeptide motif (DDL) that regulates LOX-1-mediated endocytosis of OxLDL. Taken together, these findings indicate that LOX-1 is internalised by a clathrin-independent and dynamin-2-dependent pathway and is thus likely to mediate OxLDL trafficking in vascular tissues.
PPARγ accelerates cellular senescence by inducing p16INK4α expression in human diploid fibroblasts
Authors: Gan Qini , Huang Jing , Zhou Rui , Niu Jing , Zhu Xiaojun , Wang Jing , Zhang Zongyu , Tong Tanjun
Published: June 2008

Peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in the inhibition of cell growth by promoting cell-cycle arrest, and PPARγ activation induces the expression of p16INK4α (CDKN2A), an important cell-cycle inhibitor that can induce senescence. However, the role of PPARγ in cellular senescence is unknown. Here, we show that PPARγ promotes cellular senescence by inducing p16INK4α expression. We found several indications that PPARγ accelerates cellular senescence, including enhanced senescence-associated (SA)-β-galactosidase staining, increased G1 arrest and delayed cell growth in human fibroblasts. Western blotting studies demonstrated that PPARγ activation can upregulate the expression of p16INK4α. PPARγ can bind to the p16 promoter and induce its transcription, and, after treatment with a selective PPARγ agonist, we observed more-robust expression of p16INK4α in senescent cells than in young cells. In addition, our data indicate that phosphorylation of PPARγ decreased with increased cell passage. Our results provide a possible molecular mechanism underlying the regulation of cellular senescence.
ArabidopsisSMG7 protein is required for exit from meiosis
Authors: Riehs Nina , Akimcheva Svetlana , Puizina Jasna , Bulankova Petra , Idol Rachel A. , Siroky Jiri , Schleiffer Alexander , Schweizer Dieter , Shippen Dorothy E. , Riha Karel
Published: June 2008

Meiosis consists of two nuclear divisions that are separated by a short interkinesis. Here we show that the SMG7 protein, which plays an evolutionarily conserved role in nonsense-mediated RNA decay (NMD) in animals and yeast, is essential for the progression from anaphase to telophase in the second meiotic division in Arabidopsis. Arabidopsis SMG7 is an essential gene, the disruption of which causes embryonic lethality. Plants carrying a hypomorphic smg7 mutation exhibit an elevated level of transcripts containing premature stop codons. This suggests that the role of SMG7 in NMD is conserved in plants. Furthermore, hypomorphic smg7 alleles render mutant plants sterile by causing an unusual cell-cycle arrest in anaphase II that is characterized by delayed chromosome decondensation and aberrant rearrangement of the meiotic spindle. The smg7 phenotype was mimicked by exposing meiocytes to the proteasome inhibitor MG115. Together, these data indicate that SMG7 counteracts cyclin-dependent kinase (CDK) activity at the end of meiosis, and reveal a novel link between SMG7 and regulation of the meiotic cell cycle.
Managing the Inventory of an Item with a Replacement Warranty
Authors: Huang Wei , Kulkarni Vidyadhar , Swaminathan Jayashankar M.
Published: June 2008

In this paper, we study a firm that faces demand from two sources: demand for new items and demand to replace failed items under warranty. We model this setting as a multiperiod single-product inventory problem where the demands for new items in different periods are independent and the demands for replacing failed items depend on the number and ages of the items under warranty. We consider backlogging and emergency supply cases, and study both discounted cost and average cost criteria. We prove the optimality of the w-dependent base-stock ordering policy where the base-stock level is a function of w, the vector representing the number of items at different ages currently under warranty. For the special case where the demand for new products is identically distributed, we prove the optimality of a stationary w-dependent base stock policy for the finite-horizon discounted and the infinite-horizon discounted and average cost cases. In our computational study, we find that an optimal w-dependent policy can lead to 69% average improvement in expected costs when compared to a policy that neglects demands from items under warranty.
Modeling a Presidential Prediction Market
Authors: Chen M. Keith , Ingersoll Jonathan E. , Kaplan Edward H.
Published: June 2008

Prediction markets now cover many important political events. The 2004 presidential election featured an active online prediction market at Intrade.com, where securities addressing many different election-related outcomes were traded. Using the 2004 data from this market, we examined three alternative models for these security prices, with special focus on the electoral college rules that govern U.S. presidential elections to see which models are more (or less) consistent with the data. The data reveal dependencies in the evolution of the security prices across states over time. We show that a simple diffusion model provides a good description of the overall probability distribution of electoral college votes, and an even simpler ranking model provides excellent predictions of the probability of winning the presidency. Ignoring dependencies in the evolution of security prices across states leads to considerable underestimation of the variance of the number of electoral college votes received by a candidate, which in turn leads to overconfidence in predicting whether that candidate will win the election. Overall, the security prices in the Intrade presidential election prediction market appear jointly consistent with probability models that satisfy the rules of the electoral college.
Service Adoption and Pricing of Content Delivery Network (CDN) Services
Authors: Hosanagar Kartik , Chuang John , Krishnan Ramayya , Smith Michael D.
Published: June 2008

Content delivery networks (CDNs) are a vital component of the Internet's content delivery value chain, servicing nearly a third of the Internet's most popular content sites. However, in spite of their strategic importance, little is known about the optimal pricing policies or adoption drivers of CDNs. We address these questions using analytic models of CDN pricing and adoption under Markovian traffic and extend the results to bursty traffic using numerical simulations.

When traffic is Markovian, we find that CDNs should provide volume discounts to content providers. In addition, the optimal pricing policy entails lower emphasis on value-based pricing and greater emphasis on cost-based pricing as the relative density of content providers with high outsourcing costs increases. However, when traffic is bursty and content providers have varying levels of traffic burstiness, volume discounts may be suboptimal and may even be replaced by volume taxes. Finally, when there is heterogeneity in burstiness across content providers, a pricing policy that accounts for both the mean and variance in traffic such as percentile-based pricing is more profitable than traditional volume-based pricing (metering bytes delivered in a given time window). This finding is in contrast to the current practices of many CDN firms that use traditional volume-based pricing.
Benders Decomposition for Hub Location Problems with Economies of Scale
Authors: de Camargo Ricardo Saraiva , de Miranda Gilberto , Luna Henrique Pacca L.
Published: June 2008

When considering hub-and-spoke networks with multiple allocation, the classical models of the literature compute solutions with large discount factors for small flows on interhub connections. Addressing the economies of scale issue, a tighter formulation for this problem is presented, bringing forward a special structure. A specialized version of Benders decomposition is then developed to solve large instances in reasonable time.
Association Between Hospitalization and Discontinuity of Medication Therapy Used in the Community Setting in the Netherlands
Authors: Stuffken Rutger , Heerdink Eibert R , Koning Fred HP de , Souverein Patrick C , Egberts Antoine CG
Published: June 2008

Background:

Transitions from one healthcare setting to another often parallel transitions in health status and can be associated with intentional as well as unintentional changes in patient care. Hospitalization may put patients at increased risk of discontinuity of medication use.

Objective:

To assess the association between hospitalization and medication therapy discontinuities.

Methods:

A retrospective follow-up study was conducted using data obtained from the PHARMO Record Linkage System. We randomly selected patients who had been hospitalized (index date) between July 1, 1998, and June 30, 2000. For each hospitalized patient, one nonhospitalized patient was matched for age, sex, and geographic area, and was assigned the same index date as the corresponding hospitalized patient. The primary study outcome was the incidence of one or more medication therapy discontinuities at the index date and at several control moments during a period of 18 months before and 18 months after hospital admission. We defined 4 mutually exclusive types of discontinuities: generic–brand substitution, product substitution, therapeutic switch, and stop.

Results:

The study population comprised 8681 hospitalized patients and an equal number of age/sex-matched nonhospitalized patients. Of all hospitalized patients on drug therapy at the index date (n = 5265) 3322 (63.1 %) had one or more medication therapy discontinuities at the index dale, compared with 1390 (33.5%) of the nonhospitalized patients taking medication at the index date (n = 4147; RR 1.82; 95% CI 1.71 to 1.94). The highest risk estimate was found for therapeutic switch (RR 5.34; 95% CI 3.93 to 7.26), followed by product substitution (RR 2.32; 95% CI 1.88 to 2.86) and stop (RR 1.98; 95% CI 1.85 to 2.13). There was no significantly increased risk for generic-brand name substitution (RR 0.87; 95% CI 0.72 to 1.06).

Conclusions:

Hospitalization is associated with discontinuity of drugs used in the community setting. Medication stops were observed most frequently. Hospital safety programs should focus attention on medication therapy discontinuities at times of transition to ensure continuity of care in relation to drug therapy.
Stages of change in dialectical behaviour therapy for borderline personality disorder
Authors: Soler Joaquim , Trujols Joan , Pascual Juan Carlos , Portella Maria J. , Barrachina Judith , Campins Josefa , Tejedor Rosa , Alvarez Enrique , Pérez Victor
Published: June 2008

Objectives

The study aims at evaluating the suitability of applying the transtheoretical model (TTM) stage‐of‐change construct to the treatment with dialectical behaviour therapy (DBT) of borderline personality disorder (BPD).

Design

Stages of change were assessed by means of the University of Rhode Island Change Assessment (URICA) scale prior to and after 3 months DBT skills group psychotherapy.

Method

The sample was comprised of 79 people with BPD (86% of females) at pre‐treatment, and 42 patients (80% of females) at post‐treatment. All patients were referred from clinical services and diagnosed by means of two semi‐structured interviews.

Results

In pre‐treatment assessment, precontemplation scores correlated significantly and negatively with the other subscales (contemplation, action, and maintenance) and these three subscales also correlated significantly and positively with each other. The precontemplation stage was directly related to drop‐out from the DBT group. The action subscale and the committed action (CA) composite score were significantly higher by the end of the DBT group treatment. However, with the absence of a control group it cannot be assured that these increases were directly related to DBT intervention.

Conclusions

In this observational design the stages of change of TTM seemed applicable to the DBT conceptualization of BPD and could further our understanding of the process of change in people with BPD treated with DBT.