bluuebunny/crossref_metadata_2025 huggingface dataset:
Haptoglobin Polymorphism as a Risk Factor for Chronic Kidney Disease: A Case-Control Study
Authors: Chen Yi-Chun , Lee Ching-Chih , Huang Chih-Yuan , Huang Hsien-Bin , Yu Chi-Chia , Ho Yu-Chen , Su Yu-Chieh
Published: May 2011

Aims: Taiwan has the highest incidence and prevalence of end-stage renal disease worldwide. Haptoglobin (Hp) has a role in renal protection, and there are known differences in the function of different Hp alleles. We aim to study the association between Hp genotype and chronic kidney disease (CKD) in Taiwan. Methods: We performed one hospital-based, age-matched case-control study of 213 patients with CKD and 213 controls to evaluate the association between Hp polymorphism and CKD. Three major Hp genotypes were determined using polymerase chain reaction and electrophoresis. An unconditional logistic regression model was used to identify the associated risk factors for the development of CKD. Results: The frequency of Hp2-2 genotype and Hp2 allele was significantly higher in the CKD group than in controls (p = 0.032 and 0.024, respectively). After adjustment for covariates, the Hp2-2 genotype (vs. Hp1-1; OR 3.841) remained significantly associated with the development of CKD, together with diabetes (OR 3.131), hypertension (OR 1.748) and dyslipidemia (OR 1.646). Conclusion: This present study shows that Hp2-2 genotype is an independent risk factor for CKD. Determination of the Hp genotype may be of potential value to the prediction of genetic risk for CKD.
Attenuated Cardiovascular Response to Sympathetic System Activation during Exercise in Patients with Dialysis-Induced Hypotension
Authors: Fotbolcu Hakan , Duman Dursun , Ecder Sebahat Alısır , Oduncu Vecih , Cevik Cihan , Tigen Kursat , Şirin Gokce , Özker Emre , Kıran Burak , Basaran Yelda
Published: May 2011

Background: We wished to investigate potential causes of dialysis-induced hypotension (DIH), including the attenuated cardiovascular response to sympathetic system activation during exercise and myocardial dysfunction. Methods: This study included 26 end-stage renal disease (ESRD) patients with DIH, 30 ESRD patients without DIH (Non-DIH), and 30 control subjects. Each patient was evaluated with echocardiography and a symptom-limited treadmill stress test. The chronotropic index (CRI), heart rate recovery (HRR), systolic blood pressure response to exercise (SBP response), and tissue Doppler systolic myocardial velocities were calculated. Results: The HRR and velocities were reduced in dialysis patients compared to controls; however, they were similar in patients with and without DIH. Patients with DIH had the lowest CRI compared to theNon-DIH group (0.62 ± 0.15 vs. 0.73 ± 0.17, p = 0.020) and controls (0.62 ± 0.15 vs. 0.86 ± 0.11, p < 0.001). Similarly, patients with DIH had the lowest SBP response values compared to the Non-DIH (34.88 ± 15.01 vs. 55.67 ± 25.42, p = 0.002) and controls (34.88 ± 15.01 vs. 59.70 ± 23.04, p < 0.001). Conclusion: Patients with DIH have inadequate sympathetic activity of the cardiovascular system during exercise and impaired left ventricular systolic function. Both factors could contribute to the development of hypotension during hemodialysis.
Incomplete Recovery of Myocyte Contractile Function Despite Improvement of Myocardial Architecture With Left Ventricular Assist Device Support
Authors: Ambardekar Amrut V. , Walker John S. , Walker Lori A. , Cleveland Joseph C. , Lowes Brian D. , Buttrick Peter M.
Published: May 2011

Background—

Unloading a failing heart with a left ventricular assist device (LVAD) can improve ejection fraction (EF) and LV size; however, recovery with LVAD explantation is rare. We hypothesized that evaluation of myocyte contractility and biochemistry at the sarcomere level before and after LVAD may explain organ-level changes.

Methods and Results—

Paired LV tissue samples were frozen from 8 patients with nonischemic cardiomyopathy at LVAD implantation (before LVAD) and before cardiac transplantation (after LVAD). These were compared with 8 nonfailing hearts. Isolated skinned myocytes were purified and attached to a force transducer, and dimensions, maximum calcium-saturated force, calcium sensitivity, and myofilament cooperativity were assessed. Relative isoform abundance and phosphorylation levels of sarcomeric contractile proteins were measured. With LVAD support, the unloaded EF improved (10.0±1.0% to 25.6±11.0%,
P
=0.007), LV size decreased (LV internal dimension at end diastole, 7.6±1.2 to 4.9±1.4 cm;
P
<0.001), and myocyte dimensions decreased (cross-sectional area, 1247±346 to 638±254 μm
2
;
P
=0.001). Maximum calcium-saturated force improved after LVAD (3.6±0.9 to 7.3±1.8 mN/mm
2
,
P
<0.001) implantation but was still lower than in nonfailing hearts (7.3±1.8 versus 17.6±1.8 mN/mm
2
,
P
<0.001). An increase in troponin I (TnI) phosphorylation after LVAD implantation was noted, but protein kinase C phosphorylation of TnI decreased. Biochemical changes of other sarcomeric proteins were not observed after LVAD.

Conclusions—

There is significant improvement in LV and myocyte size with LVAD, but there is only partial recovery of EF and myocyte contractility. LVAD support was associated only with biochemical changes in TnI, suggesting that alternate mechanisms might contribute to contractile changes after LVAD and that additional interventions may be needed to alter biochemical remodeling of the sarcomere to further enhance myofilament and organ-level recovery.
Estimation of Total Incremental Health Care Costs in Patients With Atrial Fibrillation in the United States
Authors: Kim Michael H. , Johnston Stephen S. , Chu Bong-Chul , Dalal Mehul R. , Schulman Kathy L.
Published: May 2011

Background—

Detailed information on the cost burden of atrial fibrillation (AF) is limited. To provide an up-to-date estimate of the national cost of AF, we conducted a retrospective, observational cohort study using administrative claims from the MarketScan Commercial and Medicare Supplemental research data bases, 2004 to 2006.

Methods and Results—

Patients aged ≥20 years with ≥1 inpatient or ≥2 outpatient AF diagnoses in 2005 (first diagnosis=index) and ≥12 months' enrollment before and after index were selected. AF patients were propensity score–matched (1:1) with non-AF control subjects. Medical costs (2008 US$), including AF costs, other cardiovascular, and noncardiovascular costs, were examined over 1 year after index. National incremental costs of AF were based on age-/sex-specific AF prevalence projections for 2010. In total, 89 066 AF patients were matched to non-AF control subjects. Over 1 year, 37.5% of AF versus 17.5% of control subjects were hospitalized and 2.1% versus 0.1% died during hospitalization. For AF versus control subjects, mean annual inpatient costs per patient were $7841 versus $2622 (incremental cost, $5218), outpatient medical costs were $9225 versus $5629 ($3596), and outpatient pharmacy costs were $3605 versus $3714 (−$109) (all
P
<0.001). The total incremental cost of AF was $8705 per patient. The national incremental cost of AF was $26.0 billion (AF, $6.0 billion; other cardiovascular, $9.9 billion; noncardiovascular, $10.1 billion). Cardiovascular costs were based on claims with a primary disease diagnosis and may be underestimates.

Conclusions—

On the basis of current US age- and sex-specific prevalence data, the national incremental AF cost is estimated to range from $6.0 to $26.0 billion.
How Well Do Large-Scale Models Reproduce Regional Hydrological Extremes in Europe?
Authors: Prudhomme Christel , Parry Simon , Hannaford Jamie , Clark Douglas B. , Hagemann Stefan , Voss Frank
Published: May 2011

This paper presents a new methodology for assessing the ability of gridded hydrological models to reproduce large-scale hydrological high and low flow events (as a proxy for hydrological extremes) as described by catalogues of historical droughts [using the regional deficiency index (RDI)] and high flows [regional flood index (RFI)] previously derived from river flow measurements across Europe. Using the same methods, total runoff simulated by three global hydrological models from the Water Model Intercomparison Project (WaterMIP) [Joint U.K. Land Environment Simulator (JULES), Water Global Assessment and Prognosis (WaterGAP), and Max Planck Institute Hydrological Model (MPI-HM)] run with the same meteorological input (watch forcing data) at the same spatial 0.5° grid was used to calculate simulated RDI and RFI for the period 1963–2001 in the same European regions, directly comparable with the observed catalogues. Observed and simulated RDI and RFI time series were compared using three performance measures: the relative mean error, the ratio between the standard deviation of simulated over observed series, and the Spearman correlation coefficient. Results show that all models can broadly reproduce the spatiotemporal evolution of hydrological extremes in Europe to varying degrees. JULES tends to produce prolonged, highly spatially coherent events for both high and low flows, with events developing more slowly and reaching and sustaining greater spatial coherence than observed—this could be due to runoff being dominated by slow-responding subsurface flow. In contrast, MPI-HM shows very high variability in the simulated RDI and RFI time series and a more rapid onset of extreme events than observed, in particular for regions with significant water storage capacity—this could be due to possible underrepresentation of infiltration and groundwater storage, with soil saturation reached too quickly. WaterGAP shares some of the issues of variability with MPI-HM—also attributed to insufficient soil storage capacity and surplus effective precipitation being generated as surface runoff—and some strong spatial coherence of simulated events with JULES, but neither of these are dominant. Of the three global models considered here, WaterGAP is arguably best suited to reproduce most regional characteristics of large-scale high and low flow events in Europe. Some systematic weaknesses emerge in all models, in particular for high flows, which could be a product of poor spatial resolution of the input climate data (e.g., where extreme precipitation is driven by local convective storms) or topography. Overall, this study has demonstrated that RDI and RFI are powerful tools that can be used to assess how well large-scale hydrological models reproduce large-scale hydrological extremes—an exercise rarely undertaken in model intercomparisons.
Consequences of Parental Divorce for Child Development
Authors: Kim Hyun Sik
Published: May 2011

In this article, I propose a three-stage estimation model to examine the effect of parental divorce on the development of children’s cognitive skills and noncognitive traits. Using a framework that includes pre-, in-, and post-divorce time periods, I disentangle the complex factors affecting children of divorce. I use the Early Childhood Longitudinal Study-Kindergarten Class 1998 to 1999 (ECLS-K), a multiwave longitudinal dataset, to assess the three-stage model. To evaluate the parameters of interest more rigorously, I employ a stage-specific ordinary least squares (OLS) model, a counterfactual matching estimator, and a piece-wise growth curve model. Within some combinations of developmental domains and stages, in particular from the in-divorce stage onward, I find negative effects of divorce even after accounting for selection factors that influence children’s skills and traits at or before the beginning of the dissolution process. These negative outcomes do not appear to intensify or abate in the ensuing study period.
Enhancing the Algorithm for Developmental–Behavioral Surveillance and Screening in Children 0 to 5 Years
Authors: Marks Kevin P. , Page Glascoe Frances , Macias Michelle M.
Published: May 2011

Objective: To determine if the 2006 American Academy of Pediatrics developmental surveillance and screening algorithm is adequate or if revisions are needed. Methods: A comprehensive literature search was conducted to investigate a clinician’s ability to perform developmental—behavioral surveillance in children 0 to 5 years. Results: Even when a broad-band developmental screen is typical, pediatricians should refer when they confidently suspect a delay but be far more suspicious about children who seem asymptomatic. Periodic screening enhances surveillance by improving early detection and early intervention (EI) eligibility rates. Nevertheless, children with concerning screens are not consistently referred and interlinked to EI. Once referred, approximately half are deemed EI-ineligible, even though they typically perform well below average and have numerous, predictive academic and psychosocial risk factors. Meanwhile, clinicians struggle with tracking at-risk children. Conclusion: Revisions are needed to optimize early detection, prevention, and monitoring. Greater emphasis is needed on developmental—behavioral promotion and referral care coordination.
Disneyfication and Localisation: The Cultural Globalisation Process of Hong Kong Disneyland
Authors: Choi Kimburley
Published: May 2011

Hong Kong Disneyland (HKDL) was seen as the ‘Millennium Dream Comes True!’ in 1999, but as ‘Hong Kong’s shame’ after its opening in 2005. In this article, interviews and ethnographic research are used to examine the different positions of various actors (HKDL workers, consumers and media practitioners) in their relationship with HKDL. Appropriating Lefebvre’s conceptual triad of space, these stories show that Disney brought Hong Kong a physical park, non-transparent values and related management practices. These same stories also demonstrate that HKDL workers and visitors work and consume the park in a local way that Disneyland management finds difficult to control; local people produce and circulate the changed meanings of ‘Disney’ and change certain Disney management policies.
Cultural Industries in Small-sized Canadian Cities
Authors: Denis-Jacob Jonathan
Published: May 2011

This paper looks at the residential location of cultural workers in the smallest Canadian cities, with the primary goal of understanding the factors making some more successful than others in attracting them. The study examines employment in 13 cultural industries in 109 small Canadian urban areas using data drawn from the 2006 Canadian census. Six explanatory factors are put forward and entered into a regression model to explain the location of cultural workers in small places: size, location with respect to metropolitan areas, work structure, amenities, elderly populations and public-sector choices. The results suggest that, beyond industry-specific production processes, the location of cultural workers in small cities is also driven by residential and lifestyle preferences.
Urban Policy Engagement with Social Sustainability in Metro Vancouver
Authors: Holden Meg
Published: May 2011

This article presents an analysis of social sustainability in comparative theoretical context and as a challenge to the post-political interpretation of sustainability in policy practice at the urban and regional scales. Metro Vancouver provides a case study for improving our understanding of the meaning of social sustainability as a framework for social policy in that it is among the handful of cities around the world currently working to define and enact social sustainability in governance terms. Results of this participant research provide evidence that some cities are politically engaging alternative development pathways using the concept of social sustainability. For sustainable development to retain its promise as an alternative policy framework for cities, social sustainability must be at the forefront.
The Fundamental Need to Belong
Authors: Lavigne Geneviève L. , Vallerand Robert J. , Crevier-Braud Laurence
Published: May 2011

The need for belongingness (the universal need to form and maintain positive, stable interpersonal relationships) has led to much research over the past decade. Although such a need is universal, some qualitative differences exist in its orientation. Specifically, two belongingness need orientations are proposed: a growth orientation (a belongingness need directed toward interpersonal actualization) and a deficit-reduction orientation (a belongingness need directed toward interpersonal deficit reduction or repair). It is hypothesized that a deficit-reduction orientation to the need to belong is associated with lower levels of intrapersonal and interpersonal psychological functioning compared to a growth orientation. The results of a series of four studies supported the proposed hypotheses. Implications of the proposed model for future research on the need to belong are discussed.
Vitamin D Deficiency in Patients Receiving Home Parenteral Nutrition
Authors: Thomson Patti , Duerksen Donald R.
Published: May 2011

Background: In addition to its role in bone metabolism, vitamin D has important immunomodulatory and antineoplastic effects. Patients on home parenteral nutrition (HPN) receive most of their vitamin D from intravenous (IV) supplementation. Vitamin D deficiency is common in the general population, and the adequacy of vitamin D supplementation in HPN patients is unclear. The purpose of this study is to determine the vitamin D status of patients on HPN. Methods: Consecutive patients seen in a regional home nutrition program had their oral and IV vitamin D intakes determined. Plasma 25‐hydroxyvitamin D levels were measured in all patients. Intake of calcium, magnesium, and phosphate were also determined. Results: The mean 25‐hydroxyvitamin D level in 22 patients receiving HPN for a mean of 33.5 months (range, 1–177) was 42 nmol/L. Vitamin D deficiency was present in 15 (68%) patients and vitamin D insufficiency in 6 (27%) patients. The mean dietary vitamin D intake was 79.5 IU per day, while the mean IV supplementation was 166 IU per day. Conclusions: In this study of a regional Canadian HPN program, there was a high prevalence of vitamin D deficiency/insufficiency affecting virtually all patients. All patients receiving HPN should be supplemented with vitamin D and have their 25‐hydroxyvitamin D levels monitored. Further studies are required to determine optimal methods and dosing of vitamin D replacement using oral supplements or ultraviolet light therapy.
Studies on the cycling, processing and programming of an industrially applicable shape memory polymer Tecoflex® (or TFX EG 72D)
Authors: Schmidt Christina , Chowdhury A. M. Sarwaruddin , Neuking Klaus , Eggeler Gunther
Published: May 2011

The present investigations were undertaken to find out whether and how often cycling, processing and programming can be repeated, whether repeated programming affects the one way effect and how much irreversible strain the shape memory polymeric material accumulates at a particular temperature. The effect was investigated in dependence of different stress levels, and the effect of both recovery temperature and recovery time was considered. As a model material the commercially and industrially applicable amorphous shape memory polymer Tecoflex® was examined and subjected to 50 programming cycles. Tecoflex® is characterized by a glass transition temperature, Tg, of 74 °C, above which it looses all its strength. During tensile testing at 20 °C (T < Tg), stresses a steady increase to 26 MPa as strains approached the rupture strain of 25%. It is observed that at 60 °C (T < Tg, but near Tg) the material can be strained to more than 2500% before rupture occurs while stresses slowly increase to values less than 0.3 MPa. It turns out that programming, cooling, unloading and heating to trigger the one way effect causes an increase of irreversible strain that is associated with a corresponding decrease of the intensity of the one way effect during the first thermomechanical cycles.
Synthesis, characterization and optical properties of distyrylanthracene-based polymers
Authors: Hriz Khaled , Chemli Mejed , Jaballah Nejmeddine , Fave Jean-Louis , Majdoub Mustapha
Published: May 2011

Distyryl- and nitrodistyrylanthracene-based polymers (P1 and P2, respectively) have been synthesized and characterized. The polymers are fully soluble in common organic solvents and have number-average molecular weights of 18 570 and 23 480 g mol−1 for P1 and P2, respectively. The optical properties of the polymers were investigated by UV-visible absorption and photoluminescence spectroscopies. The optical gaps were estimated from the absorption-onsets of the polymer films; their values were 2.79, 2.75 eV for P1 and P2, respectively. A blue photoluminescence was observed in dilute solution. In solid thin film, Π–Π interactions influence the optical properties, and red-shifted photoluminescence spectra were obtained; a green emission (573 nm) for P1 and an orange one (605 nm) for P2 were observed. The HOMO and LUMO levels were estimated using cyclic voltammetry analysis. Single-layer devices of the indium-tin oxide/polymer/aluminum configuration were fabricated and showed relatively low turn-on voltages (5.14 V for P1 and 5.00 V for P2).
Apaches Without and Enemies Within: The US Army in New Mexico, 1879—1881
Authors: Watt Robert N.
Published: May 2011

When attempting to confront hostile Apache guerrillas in New Mexico between 1879 and 1881, the US Army encountered a style of warfare which took merciless advantage of its weaknesses. However, the failure of the army to defeat its enemies can be only partially ascribed to this factor. Its efforts were further hampered by the political context within which it had to operate. Nevertheless, these factors occasionally worked in the army’s favour. When these political constraints did undermine efforts to defeat the Apaches, the US Army demonstrated that it was sometimes capable of turning this political context to its advantage.
Faultlines, Fairness, and Fighting: A Justice Perspective on Conflict in Diverse Groups
Authors: Spell Chester S. , Bezrukova Katerina , Haar Jarrod , Spell Christopher
Published: May 2011

Most people can recall instances at work where thankless tasks get in the way of tasks that lead to big rewards. This typically leads people in a group to a struggle with others over how to approach their work and set priorities. Inspired by such conversations with many employees, we develop a theory to understand how task conflict can be linked to distributive injustice. Using a survey from 42 workgroups, we found that the effect of distributive injustice on task conflict was mediated via role conflict. Group faultlines moderated this mediated relationship such as it was weaker when faultlines were stronger.
Chemical and Mechanistic Toxicology Evaluation of Exon Skipping Phosphorodiamidate Morpholino Oligomers in mdx Mice
Authors: Sazani Peter , Ness Kirk P. Van , Weller Doreen L. , Poage Duane , Nelson Keith , Shrewsbury and Stephen B.
Published: May 2011

AVI-4658 is a phosphorodiamidate morpholino oligomer (PMO) designed to induce skipping of dystrophin exon 51 and restore its expression in patients with Duchenne muscular dystrophy (DMD). Preclinically, restoration of dystrophin in the dystrophic mdx mouse model requires skipping of exon 23, achieved with the mouse-specific PMO, AVI-4225. Herein, we report the potential toxicological consequences of exon skipping and dystrophin restoration in mdx mice using AVI-4225. We also evaluated the toxicological effects of AVI-4658 in both mdx and wild-type mice. In both studies, animals were dosed once weekly for 12 weeks up to the maximum feasible dose of 960 mg/kg per injection. Both AVI-4658 and AVI-4225 were well-tolerated at all doses. Findings in AVI-4225-treated animals were generally limited to mild renal tubular basophilia/vacuolation, without any significant changes in renal function and with evidence of reversing. No toxicity associated with the mechanism of action of AVI-4225 in a dystrophic animal was observed.
Repeat-Dose Toxicology Evaluation in Cynomolgus Monkeys of AVI-4658, a Phosphorodiamidate Morpholino Oligomer (PMO) Drug for the Treatment of Duchenne Muscular Dystrophy
Authors: Sazani Peter , Ness Kirk P. Van , Weller Doreen L. , Poage Duane W. , Palyada Kiran , Shrewsbury Stephen B.
Published: May 2011

AVI-4658 is a phosphorodiamidate morpholino oligomer (PMO) drug designed to restore dystrophin expression in a subset of patients with Duchenne muscular dystrophy (DMD). Previous reports demonstrated this clinical proof-of-principle in patients with DMD following intramuscular injection of AVI-4658. This preclinical study evaluated the toxicity and toxicokinetic profile of AVI-4658 when administered either intravenously (IV) or subcutaneously (SC) to cynomolgus monkeys once weekly over 12 weeks, at doses up to the maximum feasible dose of 320 mg/kg per injection. No drug-related effects were noted on survival, clinical observations, body weight, food consumption, opthalmoscopic or electrocardiographic evaluations, hematology, clinical chemistry, urinalysis, organ weights, and macroscopic evaluations. Drug-related microscopic renal effects were dose-dependent, apparently reversible, and included basophilic granules (minimal), basophilic tubules (minimal to moderate), and tubular vacuolation (minimal to mild). These data establish the tolerability of AVI-4658 at doses up to and including the maximum feasible dose of 320 mg/kg by IV bolus or SC injection.
Negotiating hearing disability and hearing disabled identities
Authors: Hindhede Anette Lykke
Published: May 2011

Using disability theory as a framework and social science theories of identity to strengthen the arguments, this article explores empirically how working-age adults confront the medical diagnosis of hearing impairment. For most participants hearing impairment threatens the stability of social interaction and the construction of hearing disabled identities is seen as shaped in the interaction with the hearing impaired person’s surroundings. In order to overcome the potential stigmatization the ‘passing’ as normal becomes predominant. For many the diagnosis provokes radical redefinitions of the self. The discursively produced categorization and subjectivity of senescence mean that rehabilitation technologies such as hearing aids identify a particular life-style (disabled) which determines their social significance. Thus wearing a hearing aid works against the contemporary attempt to create socially ideal bodily presentations of the self, as the hearing aid is a symbolic extension of the body’s lack of function.
Using a Community-Based Participatory Research Approach to Develop a Faith-Based Obesity Intervention for African American Children
Authors: Davis Dawnavan S. , Goldmon Moses V. , Coker-Appiah Dionne S.
Published: May 2011

Childhood obesity is a major epidemic, with African American (AA) children aged 6 to 11 years experiencing increased burden. The AA faith community has numerous assets that point to the need for the intersection of faith and health to address obesity-related racial disparities. The purpose of the Our Bodies, God’s Temples (OBGT) study was to examine diet, physical activity, and body image behaviors among AA children aged 6 to 11 years; receptivity to a faith-based obesity intervention among AA children, parents, and church leaders; and strengths and barriers of implementing a faith-based obesity curriculum in the Sunday school setting. A community-based participatory research approach was used to develop an obesity intervention to be integrated into the church Sunday school setting for AA children. A Community Advisory Network worked with researchers to develop a 12-week culturally appropriate faith-based obesity intervention. Future work will test the effectiveness of the newly created curriculum on obesity-related outcomes in AA children.
A Drive Through Web 2.0
Authors: Apatu Emma J. I. , Alperin Melissa , Miner Kathleen R. , Wiljer David
Published: May 2011

This study explored Facebook™ to capture the prevalence of driving safety promotion user groups, obtain user demographic information, to understand if Facebook™ user groups influence reported driving behaviors, and to gather a sense of perceived effectiveness of Facebook™ for driving safety promotion targeted to young adults. In total, 96 driving safety Facebook™ groups (DSFGs) were identified with a total of 33,368 members, 168 administrators, 156 officers, 1,598 wall posts representing 12 countries. A total of 85 individuals participated in the survey. Demographic findings of this study suggest that driving safety promotion can be targeted to young and older adults. Respondents’ ages ranged from 18 to 66 years. A total of 62% of respondents aged ≤24 years and 57.8% of respondents aged ≥25 years reported changing their driving-related behaviors as a result of reading information on the DSFGs to which they belonged. A higher proportion of respondents ≥25 years were significantly more likely to report Facebook™ and YouTube™ as an effective technology for driving safety promotion. This preliminary study indicates that DSFGs may be effective tools for driving safety promotion among young adults. More research is needed to understand the cognition of Facebook™ users as it relates to adopting safe driving behavior. The findings from this study present descriptive data to guide public health practitioners for future health promotion activities on Facebook™.
Prophylactic transfer of BCR-ABL–, PR1-, and WT1-reactive donor T cells after T cell–depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia
Authors: Bornhäuser Martin , Thiede Christian , Platzbecker Uwe , Kiani Alexander , Oelschlaegel Uta , Babatz Jana , Lehmann Doris , Hölig Kristina , Radke Jörgen , Tuve Sebastian , Wermke Martin , Wehner Rebekka , Jähnisch Hanka , Bachmann Michael P. , Rieber E. Peter , Schetelig Johannes , Ehninger Gerhard , Schmitz Marc
Published: May 2011

Donor lymphocyte infusions have been effective in patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation, but their use is associated with the risk of graft-versus-host disease. We investigated the effects of prophylactic infusion of in vitro-generated donor T cells reactive against peptides derived from CML-associated antigens. Fourteen CML patients received conditioning therapy followed by CD34+-selected peripheral blood stem cells from matched siblings (n = 7) or unrelated (n = 7) donors. Donor-derived mature dendritic cells generated in vitro from CD14+ monocytes were loaded with human leukocyte Ag-restricted peptides derived from PR1, WT1, and/or B-cell receptor–ABL and used to repetitively stimulate donor CD8+ T cells in the presence of IL-2 and IL-7. Stimulated T cells were infused 28, 56, and 112 days after transplantation. Thirteen patients are alive and 7 remain in molecular remission (median follow-up, 45 months). Interestingly, all 4 patients receiving CD8+ T cells displaying marked cytotoxic activity in vitro and detectable peptide-reactive CD8+ T cells during follow-up have not experienced graft-versus-host disease or relapse. Our study reveals that prophylactic infusion of allogeneic CD8+ T cells reactive against peptides derived from CML-associated antigens is a safe and promising therapeutic strategy. This trial was registered at www.clinicaltrials.gov as #NCT00460629.
Calcineurin-dependent negative regulation of CD94/NKG2A expression on naive CD8+ T cells
Authors: Cho Jae-Ho , Kim Hee-Ok , Webster Kylie , Palendira Mainthan , Hahm Bumsuk , Kim Kyu-Sik , King Cecile , Tangye Stuart G. , Sprent Jonathan
Published: May 2011

Immune responses lead to expression of immunoregulatory molecules on T cells, including natural killer (NK) receptors, such as CD94/NKG2A on CD8+ T cells; these receptors restrain CD8+ responses, thereby preventing T-cell exhaustion in chronic infections and limiting immunopathology. Here, we examined the requirements for inducing CD94/NKG2A on T cells responding to antigen. In vitro, moderate induction of CD94/NKG2A expression occurred after exposure of naive CD8+ (but not CD4+) cells to CD3 ligation or specific peptide. Surprisingly, expression was inhibited by CD28/B7 costimulation. Such inhibition applied only to CD94/NKG2A and not other NK receptors (NKG2D) and was mediated by IL-2. Inhibition by IL-2 occurred via a NFAT cell-independent component of the calcineurin pathway, and CD94/NKG2A induction was markedly enhanced in the presence of calcineurin blockers, such as FK506 or using calcineurin-deficient T cells, both in vitro and in vivo. In addition to CD28-dependent inhibition by IL-2, CD94/NKG2A expression was impaired by several other cytokines (IL-4, IL-23, and transforming growth factor-β) but enhanced by others (IL-6, IL-10, and IL-21). The complex interplay between these various stimuli may account for the variable expression of CD94/NKG2A during responses to different pathogens in vivo.
A genome-wide association study reveals evidence of association with sarcoidosis at6p12.1
Authors: Hofmann S. , Fischer A. , Till A. , Müller-Quernheim J. , Häsler R. , Franke A. , Gäde K.I. , Schaarschmidt H. , Rosenstiel P. , Nebel A. , Schürmann M. , Nothnagel M. , Schreiber S. ,   the GenPhenReSa Consortium
Published: May 2011

Sarcoidosis is a complex systemic inflammatory disease of unknown aetiology that is influenced by a variety of genetic and environmental factors.

To identify further susceptibility loci for sarcoidosis, a genome-wide association study (GWAS) was conducted in 381 patients and 392 control individuals based on Affymetrix 100k GeneChip data. The top 25 single-nucleotide polymorphisms (SNPs) were selected for validation in an independent study panel (1,582 patientsversus1,783 controls).

Variant rs10484410 on chromosome6p12.1was significantly associated, with a Bonferroni-corrected p-value of 2.90×10−2in the validation sample and a nominal p-value of 2.64×10−4in the GWAS. Extensive fine mapping of the novel locus narrowed down the signal to a region comprising the genesBAG2,C6orf65,KIAA1586,ZNF451andRAB23. Verification of the sarcoidosis-associated nonsynonymous SNP rs1040461 in a further independent case–control sample and quantitative mRNA expression studies point to theRAB23gene as the most likely risk factor.RAB23is proposed to be involved in antibacterial defence processes and regulation of the sonic hedgehog signalling pathway.

The identified association of the6p12.1locus with sarcoidosis implicates this locus as a further susceptibility factor and RAB23 as a potential signalling component that may open up new perspectives in the pathophysiology of sarcoidosis.
Deterioration of exercise capacity after neonatal extracorporeal membrane oxygenation
Authors: van der Cammen-van Zijp M.H.M. , Gischler S.J. , Hop W.C.J. , de Jongste J.C. , Tibboel D. , IJsselstijn H.
Published: May 2011

Extracorporeal membrane oxygenation (ECMO) provides life support in acute reversible cardiorespiratory failure. Assessment of long-term morbidity is essential to confirm survival advantage. This study aimed to assess exercise capacity in the first 12 yrs of life after neonatal ECMO, and to evaluate the effect of primary diagnosis, lung function or perinatal characteristics on exercise capacity.

120 children who, as neonates, underwent ECMO performed 191 reliable exercise tests according to the Bruce treadmill protocol at ages 5, 8 and/or 12 yrs between 2001 and 2010. Primary diagnoses were meconium aspiration syndrome (n=66), congenital diaphragmatic hernia (n=18) and other diagnoses (n=36).

At ages 5, 8 and 12 yrs, ANOVA resulted in mean±sestandard deviation score endurance time on the treadmill of -0.5±0.1, -1.1±0.1, and -1.5±0.2, respectively, all significantly less than zero (p<0.001). Exercise capacity declined significantly over time irrespective of the primary diagnosis.

Neonates treated with ECMO are at risk of decreased exercise capacity at school age. We therefore propose prolonged follow-up. Proactive advice on sports participation or referral to a physical therapist is recommended, especially when either the parents or the children themselves report impaired exercise capacity.
T-helper cell type-1 transcription factor T-bet is upregulated in pulmonary sarcoidosis
Authors: Kriegova E. , Fillerova R. , Tomankova T. , Hutyrova B. , Mrazek F. , Tichy T. , Kolek V. , du Bois R.M. , Petrek M.
Published: May 2011

Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with “sarcoidosis-associated” genes.

Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry.

Patient’s BAL cells expressed higher mRNA T-bet levels than those of controls (mean±sdfold change 3.64±1.72; p=0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p>0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor β, CXCR3 and CXCR6 (p<0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes.

In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.
Recognition of pleural mesothelioma by mucin-1(950–958)/human leukocyte antigen A*0201-specific CD8+ T-cells
Authors: Roulois D. , Vignard V. , Gueugnon F. , Labarrière N. , Grégoire M. , Fonteneau J-F.
Published: May 2011

Recent clinical investigations have demonstrated that T-cell-based immunotherapy of malignant pleural mesothelioma (MPM) could represent an alternative to the other therapeutic strategies. However, its development suffers from the lack of identified tumour antigenic targets. Mucin (MUC)1, which is expressed and recognised by cytotoxic T-cells in numerous cancer types, has not been investigated as a potential immune target in MPM. Thus, the objective of this study was to analyse MUC1 expression by MPM cells and to determine whether this antigen can be the target of cytotoxic CD8+ T-cells (cytotoxic T-lymphocytes (CTLs)).

We first evaluated the expression and glycosylation of MUC1 by MPM cell lines using different MUC1-specific monoclonal antibodies. We then obtained a CTL clone specific for a MUC1 peptide (residues 950–958) presented by human leukocyte antigen (HLA)-A*0201 and studied its interferon-γ and cytotoxic response to MPM cell lines.

We found that all MPM cell lines expressed MUC1 protein at the cell surface with different glycosylation profiles. We also observed that HLA-A*0201+ MPM cell lines are recognised and lysed by a HLA-A*0201/MUC1(950–958)-specific CTL clone independently of the MUC1 glycosylation profile.

Thus, MUC1 expression and antigen presentation by MPM cells may represent an attractive target for immunotherapeutic treatment of MPM despite its hyperglycosylated profile.
Capability and dependency in the Newcastle 85+ cohort study. Projections of future care needs
Authors: Jagger Carol , Collerton Joanna C , Davies Karen , Kingston Andrew , Robinson Louise A , Eccles Martin P , von Zglinicki Thomas , Martin-Ruiz Carmen , James Oliver FW , Kirkwood Tom BL , Bond John
Published: May 2011

Background

Little is known of the capabilities of the oldest old, the fastest growing age group in the population. We aimed to estimate capability and dependency in a cohort of 85 year olds and to project future demand for care.

Methods

Structured interviews at age 85 with 841 people born in 1921 and living in Newcastle and North Tyneside, UK who were permanently registered with participating general practices. Measures of capability included were self-reported activities of daily living (ADL), timed up and go test (TUG), standardised mini-mental state examination (SMMSE), and assessment of urinary continence in order to classify interval-need dependency. To project future demand for care the proportion needing 24-hour care was applied to the 2008 England and Wales population projections of those aged 80 years and over by gender.

Results

Of participants, 62% (522/841) were women, 77% (651/841) lived in standard housing, 13% (106/841) in sheltered housing and 10% (84/841) in a care home. Overall, 20% (165/841) reported no difficulty with any of the ADLs. Men were more capable in performing ADLs and more independent than women. TUG validated self-reported ADLs. When classified by 'interval of need' 41% (332/810) were independent, 39% (317/810) required help less often than daily, 12% (94/810) required help at regular times of the day and 8% (67/810) required 24-hour care. Of care-home residents, 94% (77/82) required daily help or 24-hour care. Future need for 24-hour care for people aged 80 years or over in England and Wales is projected to increase by 82% from 2010 to 2030 with a demand for 630,000 care-home places by 2030.

Conclusions

This analysis highlights the diversity of capability and levels of dependency in this cohort. A remarkably high proportion remain independent, particularly men. However a significant proportion of this population require 24-hour care at home or in care homes. Projections for the next 20 years suggest substantial increases in the number requiring 24-hour care due to population ageing and a proportionate increase in demand for care-home places unless innovative health and social care interventions are found.
Association of daily tar and nicotine intake with incident myocardial infarction: Results from the population-based MONICA/KORA Augsburg Cohort Study 1984 - 2002
Authors: Zhang Qiu-Li , Baumert Jens , Ladwig Karl-Heinz , Wichmann H-Erich , Meisinger Christa , Döring Angela
Published: May 2011

Background

Cigarette smoking has been shown to be one of the most important risk factors for cardiovascular diseases. However, little is known about cumulative effects of daily tar and nicotine intake on the risk of incident myocardial infarction (MI) so far. To bridge this gap, we conducted an analysis in a large prospective study from Southern Germany investigating associations of daily tar and nicotine intake with an incident MI event.

Methods

The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors.

Results

In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake.

Conclusions

The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction.
Teaching tools in Evidence Based Practice: evaluation of reusable learning objects (RLOs) for learning about Meta-analysis
Authors: Bath-Hextall Fiona , Wharrad Heather , Leonardi-Bee Jo
Published: May 2011

Background

All healthcare students are taught the principles of evidence based practice on their courses. The ability to understand the procedures used in systematically reviewing evidence reported in studies, such as meta-analysis, are an important element of evidence based practice. Meta-analysis is a difficult statistical concept for healthcare students to understand yet it is an important technique used in systematic reviews to pool data from studies to look at combined effectiveness of treatments. In other areas of the healthcare curricula, by supplementing lectures, workbooks and workshops with pedagogically designed, multimedia learning objects (known as reusable learning objects or RLOs) we have shown an improvement in students' perceived understanding in subjects they found difficult. In this study we describe the development and evaluation of two RLOs on meta-analysis. The RLOs supplement associated lectures and aim to improve students' understanding of meta-analysis in healthcare students.

Methods

Following a quality controlled design process two RLOs were developed and delivered to two cohorts of students, a Master in Public Health course and Postgraduate diploma in nursing course. Students' understanding of five key concepts of Meta-analysis were measured before and after a lecture and again after RLO use. RLOs were also evaluated for their educational value, learning support, media attributes and usability using closed and open questions.

Results

Students rated their understanding of meta-analysis as improved after a lecture and further improved after completing the RLOs (Wilcoxon paired test, p < 0.01 in all cases) Whilst the media components of the RLOs such as animations helped most students (86%) understand concepts including for example Forest plots, 93% of students rated usability and control as important to their learning. A small number of students stated they needed the support of a lecturer alongside the RLOs (7% 'Agreed' and 21% 'Neutral').

Conclusions

Meta-analysis RLOs that are openly accessible and unrestricted by usernames and passwords provide flexible support for students who find the process of meta-analysis difficult.
The influence of the dispersion method on the electrical properties of vapor-grown carbon nanofiber/epoxy composites
Authors: Cardoso Paulo , Silva Jaime , Klosterman Donald , Covas José A , van Hattum Ferrie WJ , Simoes Ricardo , Lanceros-Mendez Senentxu
Published: May 2011

The influence of the dispersion of vapor-grown carbon nanofibers (VGCNF) on the electrical properties of VGCNF/Epoxy composites has been studied. A homogenous dispersion of the VGCNF does not imply better electrical properties. In fact, it is demonstrated that the most simple of the tested dispersion methods results in higher conductivity, since the presence of well-distributed nanofiber clusters appears to be a key factor for increasing composite conductivity.

PACS: 72.80.Tm; 73.63.Fg; 81.05.Qk