bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved elastomeric seal design based on nonhomogeneous material properties
Authors: Matus Daniel A , Klamecki Barney E
Published: September 2012

The goal of this research was improving elastomeric seal performance based on seal material design. The specific seal failure mode considered was permanent deformation or compression set of O-rings, and sealing performance degradation due to this process is common to all types of elastomeric seals. The basis for seal design was identified as reducing the elastic strain energy in the seal since it drives the growth of permanent material deformation. The design concept developed was using variation of material behavior over the seal section to manipulate the level and distribution of elastic strain energy. Design studies used finite element analyses with experimentally measured material behavior to quantify effects of varying seal material characteristic on seal performance. Sealing performance was described in terms of compression set and seal-counterface contact pressure. Experimental O-rings were produced based on designs that included regions of less stiff material in the larger surrounding seal section. Performance of new design seals was compared to conventional one-material seals and improved sealing performance was demonstrated. With the modified design seals, both compression set and the rate of sealing contact pressure loss over time were decreased. There was a loss of initial maximum contact pressure with the inclusion of less stiff material regions, but it was shown that this effect can be mitigated by properly locating the softer material in the overall seal section. In summary, properly implemented material variations over the seal will result in lower strain energy content, lower rate of permanent deformation development and decreasing rate of loss of seal-counterface contact pressure.
Exit and Entrance Polling
Authors: Klofstad Casey A. , Bishin Benjamin G.
Published: September 2012

We report the results of an experiment in which voters participating in the 2008 presidential election were surveyed either as they exited their voting places (a traditional exit poll) or as they waited in line to vote (an “entrance poll”). To the best of our knowledge, the efficacy of entrance polling has not been studied previously. Our data show that the entrance poll, when compared to the exit poll, produced a significantly higher cooperation rate among voters and a significantly lower item nonresponse rate. In our discussion of these results, we examine the benefits and potential complications of entrance polling.
Policy Implications for Optimizing Advanced Practice Registered Nurse Use Nationally
Authors: Newhouse Robin P. , Weiner Jonathan P. , Stanik-Hutt Julie , White Kathleen M. , Johantgen Meg , Steinwachs Don , Zangaro George , Aldebron Jillian , Bass Eric B.
Published: September 2012

This article examines the potential benefits of enhanced use of advanced practice registered nurses (APRNs) given health care workforce projections that predict an inadequate supply of certain types of providers. The conclusions of a systematic review comparing the effectiveness of care provided by APRNs with that of physicians alone or teams without APRNs indicate the viability of this approach. Allowing APRNs to assume roles that take full advantage of their educational preparation could mitigate the shortage of primary care physicians and improve care processes. The development of health care policy should be guided by patient-centric evidence rather than how care has been delivered in the past.
Coil Embolization as a Treatment Alternative for Dialysis-Associated Steal Syndrome
Authors: Shukla Pratik A. , Contractor Sohail , Huang Joe T. , Curi Michael A.
Published: September 2012

Steal syndrome is a rare but serious complication of arteriovenous fistulas (AVF) created as well as the angioplasty technique used for its maturation and can have severe consequences if left untreated. Standard treatment options generally lead to loss of fistula access, although newer practices such as coil embolization are being utilized to conserve the AVF. Here we illustrate a case of a 65-year-old man with end-stage renal disease on dialysis, who had a Brescia-Cimino (radiocephalic) AV fistula created and subsequently underwent balloon-assisted maturation for an underdeveloped fistula. One month later, the patient presented with a cold thumb and index finger along with parasthesias in those digits and was treated with coil embolization of the distal radial artery while leaving the AVF functional. Steal syndrome and the novel treatment option of coil embolization are reviewed here.
Therapeutic misconception in research subjects: Development and validation of a measure
Authors: Appelbaum Paul S , Anatchkova Milena , Albert Karen , Dunn Laura B , Lidz Charles W
Published: September 2012

Background

Therapeutic misconception (TM), which occurs when research subjects fail to appreciate the distinction between the imperatives of clinical research and ordinary treatment, may undercut the process of obtaining meaningful consent to clinical research participation. Previous studies have found that TM is widespread, but progress in addressing TM has been stymied by the absence of a validated method for assessing its presence.

Purpose

The goal of this study was to develop and validate a theoretically grounded measure of TM, assess its diagnostic accuracy, and test previous findings regarding TM’s prevalence.

Methods

A total of 220 participants were recruited from clinical trials at four academic medical centers in the United States. Participants completed a 28-item Likert-type questionnaire to assess the presence of beliefs associated with TM, and a semistructured TM interview designed to elicit their perceptions of the nature of the clinical trial in which they were participating. Data from the questionnaires were subjected to factor analysis, and items with poor factor loadings were excluded. This resulted in a 10-item scale, with three strongly correlated factors and excellent internal consistency; the fit indices of the model across 10 training sets were consistent with the original results, suggesting a stable factor solution.

Results

The scale was validated against the TM interview, with significantly higher scores among subjects coded as displaying evidence of TM. Receiver operating curve (ROC) analysis based on a 10-fold internal cross-validation yielded area under the ROC (AUC) = 0.682 for any evidence of TM. When sensitivity (0.72) and specificity (0.61) were both optimized, positive predictive value was 0.65 and negative predictive value was 0.68, with a positive likelihood ratio of 1.89 and a negative likelihood ratio of 0.47. In all, 50.5% (n = 101) of the participants manifested evidence of TM on the TM interview, a somewhat lower rate than in most previous studies.

Limitations

The predictive value of the scale compared with the ‘gold standard’ clinical interview is modest, although similar to other instruments based on self-report assessing states of mind rather than discrete symptoms. Thus, although the scale can offer evidence of which subjects are at risk for distortions in their decisions and to what degree, it will not allow researchers to conclude definitively that TM is present in a given subject.

Conclusions

The development of a reliable and valid TM scale, even with modest predictive power, should permit investigators in clinical trials to identify subjects with tendencies to misinterpret the nature of the situation and to provide additional information to them. It should also stimulate research on how best to decrease TM and facilitate meaningful informed consent to clinical research.
A Rare Case of Tuberculosis of the Midfoot
Authors: Ferguson Kim B. , Elias Jones Cameron , Thomson Allan George , Moir John Stuart
Published: September 2012

Despite the increasing prevalence of tuberculosis in developed countries, tuberculous osteomyelitis of the foot remains an uncommon complication. The relative rarity of such a diagnosis means that delays are often incurred before clinicians can correctly identify the pathogen and therefore instigate appropriate chemotherapy. The authors present a case of midfoot pain secondary to tuberculous osteomyelitis.

Levels of Evidence: Therapeutic, Level IV: Case Study
Alemtuzumab use in relapsed and refractory chronic lymphocytic leukemia: a history and discussion of future rational use
Authors: Warner Jeremy L. , Arnason Jon E.
Published: September 2012

In this review, we outline the clinical experience with single-agent alemtuzumab as a treatment for relapsed and refractory chronic lymphocytic leukemia (CLL) in both prospective and retrospective trials and describe the multiagent use of the drug with the goal of updating clinicians on recent developments and possible future rational combinations. Alemtuzumab, an antibody targeting the lymphocyte-specific surface marker CD52, is an approved agent for the treatment of CLL. Despite its demonstrated efficacy, likely secondary to concerns regarding infectious complications, it is most commonly used in the relapsed and refractory setting. Given alemtuzumab’s unique mechanism of action it has been demonstrated to have activity in disease that is refractory to both alkylating agents and purine analogs. Furthermore, it has activity in TP53-mutated disease, which has the worst prognosis of any subset of CLL. Alemtuzumab has greater efficacy on circulating disease relative to nodal disease. Rational combinations are attempting to use these attributes to increase response rates in patients with relapsed and refractory disease.
Intermixing of metal oxide/Ag/metal oxide nanoscale multilayers prepared by rf reactive magnetron sputtering
Authors: Hasan M M , Haseeb A S M A , Masjuki H H
Published: September 2012

This study mainly aims to evaluate the intermixing between layers during the deposition of dielectric/metal/dielectric nanoscale multilayer coatings. TiO2 and WO3 films as dielectric materials are developed using radio frequency reactive magnetron sputtering on unheated soda lime glass substrates. Ag films are grown using radio frequency argon sputtering. Auger electron spectroscopy and ultraviolet–visible–near infrared spectrometry are employed to estimate the degree of layer intermixing in TiO2/Ag, WO3/Ag, TiO2/Ag/TiO2 and WO3/Ag/WO3 films. The morphological properties are also investigated under a field emission scanning electron microscope and an atomic force microscope. The transmittance curves for bilayer films exhibited heat mirror effects significantly. However, multilayer films showed a little amount of heat mirror effects. Auger electron spectroscopy depth profiles confirmed a minor diffusion of Ag at the TiO2/Ag interface. However, significant interactions of WO3 with Ag were observed for the WO3/Ag film. Besides, severe intermixing and oxidation of Ag films were observed for the multilayer films.
Characterisation of 12CaO.7Al2O3 insulator and electride doped indium tin oxide thin films for OLED applications
Authors: Jung C , Yoon D H
Published: September 2012

In this study, 12CaO.7Al2O3 (C12A7) insulator and electride doped indium tin oxide (ITO) (ITO:C12A7 insulator and electride) films were deposited on glass substrates by an radio frequency magnetron co-sputtering method with increasing number of C12A7 insulator and electride chips. The carrier concentration of both films was slightly decreased with increasing number of C12A7 insulator and electride chips to a minimum value of 7·8×1019 cm−3. On the other hand, the resistivity of the films increased gradually with increasing number of C12A7 insulator and electride chips to maximum value of 8·1×10−3 Ω cm for seven chips in the films. The decrease in carrier concentration and increase in resistivity can be related with the crystallinity of the films. The structural property and surface roughness of the films were examined and the change of grain size was strongly dependent on the decrease in crystallinity and surface roughness.
Adaptor protein Lnk binds to and inhibits normal and leukemic FLT3
Authors: Lin De-Chen , Yin Tong , Koren-Michowitz Maya , Ding Ling-Wen , Gueller Saskia , Gery Sigal , Tabayashi Takayuki , Bergholz Ulla , Kazi Julhash U. , Rönnstrand Lars , Stocking Carol , Koeffler H. Phillip
Published: September 2012

Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase with important roles in hematopoietic progenitor cell survival and proliferation. It is mutated in approximately one-third of AML patients, mostly by internal tandem duplications (ITDs). Adaptor protein Lnk is a negative regulator of hematopoietic cytokine signaling. In the present study, we show that Lnk interacts physically with both wild-type FLT3 (FLT3-WT) and FLT3-ITD through the SH2 domains. We have identified the tyrosine residues 572, 591, and 919 of FLT3 as phosphorylation sites involved in direct binding to Lnk. Lnk itself was tyrosine phosphorylated by both FLT3 ligand (FL)–activated FLT3-WT and constitutively activated FLT3-ITD. Both shRNA-mediated depletion and forced overexpression of Lnk demonstrated that activation signals emanating from both forms of FLT3 are under negative regulation by Lnk. Moreover, Lnk inhibited 32D cell proliferation driven by different FLT3 variants. Analysis of primary BM cells from Lnk-knockout mice showed that Lnk suppresses the expansion of FL-stimulated hematopoietic progenitors, including lymphoid-primed multipotent progenitors. The results of the present study show that through direct binding to FLT3, Lnk suppresses FLT3-WT/ITD–dependent signaling pathways involved in the proliferation of hematopoietic cells. Therefore, modulation of Lnk expression levels may provide a unique therapeutic approach for FLT3-ITD–associated hematopoietic disease.
Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype
Authors: Robinson Claire M , Neary Roisin , Levendale Ashleigh , Watson Chris J , Baugh John A
Published: September 2012

Background

Pulmonary fibrosis is a debilitating and lethal disease with no effective treatment options. Understanding the pathological processes at play will direct the application of novel therapeutic avenues. Hypoxia has been implicated in the pathogenesis of pulmonary fibrosis yet the precise mechanism by which it contributes to disease progression remains to be fully elucidated. It has been shown that chronic hypoxia can alter DNA methylation patterns in tumour-derived cell lines. This epigenetic alteration can induce changes in cellular phenotype with promoter methylation being associated with gene silencing. Of particular relevance to idiopathic pulmonary fibrosis (IPF) is the observation that Thy-1 promoter methylation is associated with a myofibroblast phenotype where loss of Thy-1 occurs alongside increased alpha smooth muscle actin (α-SMA) expression. The initial aim of this study was to determine whether hypoxia regulates DNA methylation in normal human lung fibroblasts (CCD19Lu). As it has been reported that hypoxia suppresses Thy-1 expression during lung development we also studied the effect of hypoxia on Thy-1 promoter methylation and gene expression.

Methods

CCD19Lu were grown for up to 8 days in hypoxia and assessed for global changes in DNA methylation using flow cytometry. Real-time PCR was used to quantify expression of Thy-1, α-SMA, collagen I and III. Genomic DNA was bisulphite treated and methylation specific PCR (MSPCR) was used to examine the methylation status of the Thy-1 promoter.

Results

Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2′-deoxycytidine. MSPCR revealed that Thy-1 became methylated following fibroblast exposure to 1% O2.

Conclusion

These data suggest that global and gene-specific changes in DNA methylation may play an important role in fibroblast function in hypoxia.
Sequencing and analysis of a South Asian-Indian personal genome
Authors: Gupta Ravi , Ratan Aakrosh , Rajesh Changanamkandath , Chen Rong , Kim Hie Lim , Burhans Richard , Miller Webb , Santhosh Sam , Davuluri Ramana V , Butte Atul J , Schuster Stephan C , Seshagiri Somasekar , Thomas George
Published: September 2012

Background

With over 1.3 billion people, India is estimated to contain three times more genetic diversity than does Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the Indian subcontinent been published at sufficient depth and coverage. In this study we have sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.

Results

We identified over 3.4 million SNPs in this genome including over 89,873 private variations. Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes. Analysis of the SAIF mitochondrial genome showed that it was closely related to the U1 haplogroup which has been previously observed in Kerala. We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases. In analyzing SNPs that modulate drug response, we found a variation that predicts a favorable response to metformin, a drug used to treat diabetes. SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin. In addition, we report the presence of several additional SNPs of medical relevance.

Conclusions

This is the first study to report the complete whole genome sequence of a female from the state of Kerala in India. The availability of this complete genome and variants will further aid studies aimed at understanding genetic diversity, identifying clinically relevant changes and assessing disease burden in the Indian population.
The lavender plumage colour in Japanese quail is associated with a complex mutation in the region of MLPH that is related to differences in growth, feed consumption and body temperature
Authors: Bed’hom Bertrand , Vaez Mohsen , Coville Jean-Luc , Gourichon David , Chastel Olivier , Follett Sarah , Burke Terry , Minvielle Francis
Published: September 2012

Background

The lavender phenotype in quail is a dilution of both eumelanin and phaeomelanin in feathers that produces a blue-grey colour on a wild-type feather pattern background. It has been previously demonstrated by intergeneric hybridization that the lavender mutation in quail is homologous to the same phenotype in chicken, which is caused by a single base-pair change in exon 1 of MLPH.

Results

In this study, we have shown that a mutation of MLPH is also associated with feather colour dilution in quail, but that the mutational event is extremely different. In this species, the lavender phenotype is associated with a non-lethal complex mutation involving three consecutive overlapping chromosomal changes (two inversions and one deletion) that have consequences on the genomic organization of four genes (MLPH and the neighbouring PRLH, RAB17 and LRRFIP1). The deletion of PRLH has no effect on the level of circulating prolactin. Lavender birds have lighter body weight, lower body temperature and increased feed consumption and residual feed intake than wild-type plumage quail, indicating that this complex mutation is affecting the metabolism and the regulation of homeothermy.

Conclusions

An extensive overlapping chromosome rearrangement was associated with a non-pathological Mendelian trait and minor, non deleterious effects in the lavender Japanese quail which is a natural knockout for PRLH.
Pregnancy loss and role of infant HIV status on perinatal mortality among HIV-infected women
Authors: Kim Hae-Young , Kasonde Prisca , Mwiya Mwiya , Thea Donald M , Kankasa Chipepo , Sinkala Moses , Aldrovandi Grace , Kuhn Louise
Published: September 2012

Background

HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status.

Methods

A total of 1229 HIV-infected pregnant women were enrolled (2001–2004) in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal (<28 days) and early mortality (<70 days) were described using Kaplan-Meier methods.

Results

The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10–3.27) and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46–6.97), and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02–1.54). The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25–6.08). Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection.

Conclusions

More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to complement necessary therapeutic and prophylactic antiretroviral interventions.
Identifying obesity indicators which best correlate with type 2 diabetes in a Chinese population
Authors: Xin Zhong , Liu Chang , Niu Wen-Yan , Feng Jian-Ping , Zhao Lei , Ma Ya-Hong , Hua Lin , Yang Jin-Kui
Published: September 2012

Background

Obesity has been shown to be a prognostic indicator of type 2 diabetes (T2D); however, the power of different obesity indicators in the detection of T2D remains controversial. This study evaluates the detecting power of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHTR) for the presence of T2D in undiagnosed diabetics among the Chinese population.

Methods

Individuals were selected from an ongoing large-scale population-based Beijing Community Pre-Diabetes (BCPD) study cohort. The oral glucose tolerance tests (OGTT) were performed to diagnose diabetes. A total of 220 new cases of T2D and 1,868 normal blood glucose subjects were analyzed. ROC curve analyses were used to compare the association of different obesity indicators with T2D and determine the optimal cut-off points of the best predictor for identifying T2D in men and women.

Results

All indicators positively correlated with presence of T2D in both men and women. In women, WC, WHR and WHTR were similar, but were better in identifying T2D when compared to BMI (P < 0.0001, P=0.0016 and P=0.0001, respectively). In men, WC, WHTR and BMI were similar, but WC and WHTR were better than WHR (P=0.0234, P=0.0101, respectively). For women, 86 cm was the optimal WC cut-off point, and its sensitivity and specificity were 0.714 and 0.616; for men, the optimal cut-off point was 90 cm, and its sensitivity and specificity were 0.722 and 0.571.

Conclusion

Compared with BMI, WHR and WHTR, WC is a simple and accurate measure for predicting T2D in the Chinese population.
Electro-acupuncture on functional peripheral nerve regeneration in mice: a behavioural study
Authors: Hoang Ngoc Son , Sar Chamroeun , Valmier Jean , Sieso Victor , Scamps Frédérique
Published: September 2012

Background

The improvement of axonal regeneration is a major objective in the treatment of peripheral nerve injuries. The aim of this study was to evaluate the effects of electro-acupuncture on the functional recovery of sensorimotor responses following left sciatic nerve crush in mice.

Methods

Sciatic nerve crush was performed on seven week old female mice. Following the injury, the control group was untreated while the experimental group received an electro-acupuncture application to the injured limb under isoflurane anesthesia at acupoints GB 30 and GB 34. Mechanical and heat sensitivity tests were performed to evaluate sensory recovery. Gait analysis was performed to assess sensorimotor recovery.

Results

Our results show that normal sensory recovery is achieved within five to six weeks with a two-week period of pain preceding the recovery to normal sensitivity levels. While electro-acupuncture did not accelerate sensory recovery, it did alleviate pain-related behaviour but only when applied during this period. Application before the development of painful symptoms did not prevent their occurrence. The analysis of gait in relation to the sensory tests suggests that the electro-acupuncture specifically improved motor recovery.

Conclusions

This study demonstrates that electro-acupuncture exerts a positive influence on motor recovery and is efficient in the treatment of pain symptoms that develop during target re-innervation.
Reducing power and iron chelating property of Terminalia chebula (Retz.) alleviates iron induced liver toxicity in mice
Authors: Sarkar Rhitajit , Hazra Bibhabasu , Mandal Nripendranath
Published: September 2012

Background

The 70% methanol extract of Terminalia chebula Retz. fruit (TCME) was investigated for its in vitro iron chelating property and in vivo ameliorating effect on hepatic injury of iron overloaded mice.

Methods

The effect of fruit extract on Fe2+-ferrozine complex formation and Fe2+ mediated pUC-18 DNA breakdown was studied in order to find the in vitro iron chelating activity. Thirty-six Swiss Albino mice were divided into six groups of: blank, patient control and treated with 50, 100, 200 mg/kg b.w. of TCME and desirox (standard iron chelator drug with Deferasirox as parent compound). Evaluations were made for serum markers of hepatic damage, antioxidant enzyme, lipid per oxidation and liver fibrosis levels. The reductive release of ferritin iron by the extract was further studied.

Results

In vitro results showed considerable iron chelation with IC50 of 27.19 ± 2.80 μg/ml, and a significant DNA protection with [P]50 of 1.07 ± 0.03 μg/ml along with about 86% retention of supercoiled DNA. Iron-dextran injection (i.p.) caused significant increase in the levels of the serum enzymes, viz., alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP) and Bilirubin, which were subsequently lowered by oral administration of 200 mg/kg b.w. dose of the fruit extract by 81.5%, 105.88%, 188.08% and 128.31%, respectively. Similarly, treatment with the same dose of the extract was shown to alleviate the reduced levels of liver antioxidant enzyme superoxide dismutase, catalase, glutathione S-transferase and non-enzymatic reduced glutathione, by 49.8%, 53.5%, 35.4% and 11% respectively, in comparison to the iron overloaded mice. At the same time, the fruit extract effectively lowered the iron-overload induced raised levels of lipid per oxidation, protein carbonyl, hydroxyproline and liver iron by 49%, 67%, 67% and 26%, respectively, with oral treatment of 200 mg/kg b.w. dose of TCME. The fruit extract also showed potential activity for reductive release of ferritin iron.

Conclusions

These findings suggest that Terminalia chebula extract may contain active substances capable of lessening iron overload induced toxicity, and hence possibly be useful as iron chelating drug for iron overload diseases.
Psychometric properties of the patient assessment of chronic illness care measure: acceptability, reliability and validity in United Kingdom patients with long-term conditions
Authors: Rick Jo , Rowe Kelly , Hann Mark , Sibbald Bonnie , Reeves David , Roland Martin , Bower Peter
Published: September 2012

Background

The Patient Assessment of Chronic Illness Care (PACIC) is a US measure of chronic illness quality of care, based on the influential Chronic Care Model (CCM). It measures a number of aspects of care, including patient activation; delivery system design and decision support; goal setting and tailoring; problem-solving and contextual counselling; follow-up and coordination. Although there is developing evidence of the utility of the scale, there is little evidence about its performance in the United Kingdom (UK). We present preliminary data on the psychometric performance of the PACIC in a large sample of UK patients with long-term conditions.

Method

We collected PACIC, demographic, clinical and quality of care data from patients with long-term conditions across 38 general practices, as part of a wider longitudinal study. We assess rates of missing data, present descriptive and distributional data, assess internal consistency, and test validity through confirmatory factor analysis, and through associations between PACIC scores, patient characteristics and related measures.

Results

There was evidence that rates of missing data were high on PACIC (9.6% - 15.9%), and higher than on other scales used in the same survey. Most PACIC sub-scales showed reasonable levels of internal consistency (alpha = 0.68 – 0.94), responses did not demonstrate high skewness levels, and floor effects were more frequent (up to 30.4% on the follow up and co-ordination subscale) than ceiling effects (generally <5%). PACIC demonstrated preliminary evidence of validity in terms of measures of long-term condition care. Confirmatory factor analysis suggested that the five factor PACIC structure proposed by the scale developers did not fit the data: reporting separate factor scores may not always be appropriate.

Conclusion

The importance of improving care for long-term conditions means that the development and validation of measures is a priority. The PACIC scale has demonstrated potential utility in this regard, but further assessment is required to assess low levels of completion of the scale, and to explore the performance of the scale in predicting outcomes and assessing the effects of interventions.
Combined metabolic engineering of precursor and co-factor supply to increase α-santalene production by Saccharomyces cerevisiae
Authors: Scalcinati Gionata , Partow Siavash , Siewers Verena , Schalk Michel , Daviet Laurent , Nielsen Jens
Published: September 2012

Background

Sesquiterpenes are a class of natural products with a diverse range of attractive industrial proprieties. Due to economic difficulties of sesquiterpene production via extraction from plants or chemical synthesis there is interest in developing alternative and cost efficient bioprocesses. The hydrocarbon α-santalene is a precursor of sesquiterpenes with relevant commercial applications. Here, we construct an efficientSaccharomyces cerevisiaecell factory for α-santalene production.

Results

A multistep metabolic engineering strategy targeted to increase precursor and cofactor supply was employed to manipulate the yeast metabolic network in order to redirect carbon toward the desired product. To do so, genetic modifications were introduced acting to optimize the farnesyl diphosphate branch point, modulate the mevalonate pathway, modify the ammonium assimilation pathway and enhance the activity of a transcriptional activator. The approach employed resulted in an overall α-santalene yield of a 0.0052 Cmmol (Cmmol glucose)-1corresponding to a 4-fold improvement over the reference strain. This strategy, combined with a specifically developed continuous fermentation process, led to a final α-santalene productivity of 0.036 Cmmol (g biomass)-1h-1.

Conclusions

The results reported in this work illustrate how the combination of a metabolic engineering strategy with fermentation technology optimization can be used to obtain significant amounts of the high-value sesquiterpene α-santalene. This represents a starting point toward the construction of a yeast “sesquiterpene factory” and for the development of an economically viable bio-based process that has the potential to replace the current production methods.
Adolescent lipoprotein classifications according to National Health and Nutrition Examination Survey (NHANES) vs. National Cholesterol Education Program (NCEP) for predicting abnormal lipid levels in adulthood in a Middle East population
Authors: Hatami Masumeh , Tohidi Maryam , Mohebi Reza , Khalili Davood , Azizi Fereidoun , Hadaegh Farzad
Published: September 2012

Background

To compare the predictive ability of adolescent lipoprotein classification using the National Examination Survey (NHANES) cut points and those of the National Cholesterol Education Program (NCEP) for predicting abnormal levels in adulthood.

Method

From 1032 adolescents, aged 14–19 years, participants of the Tehran Lipid and Glucose Study, all lipid measures were determined at baseline and again after 6 years. Multivariable Odds Ratios (ORs) were calculated for borderline and high categories of lipids to predict dyslipidemia in adulthood, considering the normal level as a reference. Area under the receiving characteristics curve (AUC) was used to assess the predictive ability of each adolescent lipid classification.

Result

Applying the NCEP classification, the prevalences of high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and low high density lipoprotein cholesterol (HDL-C) in males were 12.1%, 12.9%, 26.1% and 34.2% respectively; in females the corresponding prevalences were 15.4%, 17.9%, 21.4% and 25.0%, respectively. Using NHANES cut points, the prevalence of high TC, LDL-C and triglycerides were lower, than those defined by NCEP; the ORs of high categories of lipids (defined by NHANES) were higher than ORs based on the NECP classification, except for HDL-C. For all lipid measures, both classifications had similar predictive abilities, except for TC/HDL-C, which had higher predictive power applying the NHANES classification rather than the NCEP one (AUC 71% vs. 68%, respectively).

Conclusion

No differences were found between NCEP and NHANES classifications for prediction of adult dyslipidemia, except for TC/HDL-C. Because of their simple application, NCEP cut points can be used in clinical settings.
Is there any role of thrombin activatable fibrinolysis inhibitor in the development of a hypercoagulable state in gastric cancer
Authors: Eser Mehmet , Kement Metin , Balin Salim , Coskun Cihan , Kefeli Umut , Gumus Mahmut , Altuntas Yunus Emre , Kurt Necmi , Mayadagli Alparslan
Published: September 2012

Background

The purpose of this study was to investigate plasma levels of thrombin activatable fibrinolysis inhibitor (TAFI) and TAFI’s relationship with coagulation markers (prothrombin fragment 1 + 2) in gastric cancer patients.

Methods

Thirty-three patients with gastric adenocarcinoma and 29 healthy control subjects were prospectively enrolled in the study. Patients who had a history of secondary malignancy, thrombosis related disease, oral contraceptive use, diabetes mellitus, chronic renal failure or similar chronic metabolic disease were excluded from the study. A fasting blood sample was drawn from patients to determine the plasma levels of TAFI and Prothrombin Fragment 1 + 2 (F 1 + 2). In addition, data on patient age, sex, body mass index (BMI) and stage of disease were recorded. The same parameters, except stage of disease, were also recorded for the control group. Subsequently, we assessed the difference in the levels of TAFI and F 1 + 2 between the patient and control groups. Moreover, we investigated the relation of TAFI and F 1 + 2 levels with age, sex, BMI and stage of disease in the gastric cancer group.

Results

There were no statistical differences in any demographic variables (age, gender and BMI) between the groups (Table 1). The mean plasma TAFI levels of the gastric cancer group (69.4 ± 33.1) and control group (73.3 ± 27.5) were statistically similar (P = 0.62). The mean plasma F 1 + 2 level in the gastric cancer group was significantly higher than for those in the control group (549.7 ± 325.3 vs 151.9 ± 67.1, respectively; P < 0.001). In the gastric cancer group, none of the demographic variables (age, gender and BMI) were correlated with either TAFI or F 1 + 2 levels. Also, no significant associations were found between the stage of the cancer and either TAFI or F 1 + 2 levels.

Conclusion

In our study, TAFI levels of gastric cancer patients were similar to healthy subjects. The results of our study suggest that TAFI does not play a role in pathogenesis of the hypercoagulable state in gastric cancer patients.
Mapping global health research investments, time for new thinking - A Babel Fish for research data
Authors: Terry Robert F , Allen Liz , Gardner Charles A , Guzman Javier , Moran Mary , Viergever Roderik F
Published: September 2012

Today we have an incomplete picture of how much the world is spending on health and disease-related research and development (R&D). As such it is difficult to align, or even begin to coordinate, health R&D investments with international public health priorities.

Current efforts to track and map global health research investments are complex, resource-intensive, and caveat-laden. An ideal situation would be for all research funding to be classified using a set of common standards and definitions. However, the adoption of such a standard by everyone is not a realistic, pragmatic or even necessary goal.

It is time for new thinking informed by the innovations in automated online translation - e.g. Yahoo's Babel Fish. We propose a feasibility study to develop a system that can translate and map the diverse research classification systems into a common standard, allowing the targeting of scarce research investments to where they are needed most.
A systematic review of reliability and objective criterion-related validity of physical activity questionnaires
Authors: Helmerhorst Hendrik Hendrik JF , Brage Søren , Warren Janet , Besson Herve , Ekelund Ulf
Published: September 2012

Physical inactivity is one of the four leading risk factors for global mortality. Accurate measurement of physical activity (PA) and in particular by physical activity questionnaires (PAQs) remains a challenge. The aim of this paper is to provide an updated systematic review of the reliability and validity characteristics of existing and more recently developed PAQs and to quantitatively compare the performance between existing and newly developed PAQs.

A literature search of electronic databases was performed for studies assessing reliability and validity data of PAQs using an objective criterion measurement of PA between January 1997 and December 2011. Articles meeting the inclusion criteria were screened and data were extracted to provide a systematic overview of measurement properties. Due to differences in reported outcomes and criterion methods a quantitative meta-analysis was not possible.

In total, 31 studies testing 34 newly developed PAQs, and 65 studies examining 96 existing PAQs were included. Very few PAQs showed good results on both reliability and validity. Median reliability correlation coefficients were 0.62–0.71 for existing, and 0.74–0.76 for new PAQs. Median validity coefficients ranged from 0.30–0.39 for existing, and from 0.25–0.41 for new PAQs.

Although the majority of PAQs appear to have acceptable reliability, the validity is moderate at best. Newly developed PAQs do not appear to perform substantially better than existing PAQs in terms of reliability and validity. Future PAQ studies should include measures of absolute validity and the error structure of the instrument.
Identification of functional DNA variants in the constitutive promoter region of MDM2
Authors: Lalonde Marie-Eve , Ouimet Manon , Larivière Mathieu , Kritikou Ekaterini A , Sinnett Daniel
Published: September 2012

Although mutations in the oncoprotein murine double minute 2 (MDM2) are rare, MDM2 gene overexpression has been observed in several human tumors. Given that even modest changes in MDM2 levels might influence the p53 tumor suppressor signaling pathway, we postulated that sequence variation in the promoter region of MDM2 could lead to disregulated expression and variation in gene dosage. Two promoters have been reported for MDM2; an internal promoter (P2), which is located near the end of intron 1 and is p53-responsive, and an upstream constitutive promoter (P1), which is p53-independent. Both promoter regions contain DNA variants that could influence the expression levels of MDM2, including the well-studied single nucleotide polymorphism (SNP) SNP309, which is located in the promoter P2; i.e., upstream of exon 2. In this report, we screened the promoter P1 for DNA variants and assessed the functional impact of the corresponding SNPs. Using the dbSNP database and genotyping validation in individuals of European descent, we identified three common SNPs (−1494 G > A; indel 40 bp; and −182 C > G). Three major promoter haplotypes were inferred by using these three promoter SNPs together with rs2279744 (SNP309). Following subcloning into a gene reporter system, we found that two of the haplotypes significantly influenced MDM2 promoter activity in a haplotype-specific manner. Site-directed mutagenesis experiments indicated that the 40 bp insertion/deletion variation is causing the observed allelic promoter activity. This study suggests that part of the variability in the MDM2 expression levels could be explained by allelic p53-independent P1 promoter activity.
H2-induced copper and silver nanoparticle precipitation inside sol-gel silica optical fiber preforms
Authors: Chahadih Abdallah , El Hamzaoui Hicham , Cristini Odile , Bigot Laurent , Bernard Rémy , Kinowski Christophe , Bouazaoui Mohamed , Capoen Bruno
Published: September 2012

Ionic copper- or silver-doped dense silica rods have been prepared by sintering sol-gel porous silica xerogels doped with ionic precursors. The precipitation of Cu or Ag nanoparticles was achieved by heat treatment under hydrogen followed by annealing under air atmosphere. The surface plasmon resonance bands of copper and silver nanoparticles have been clearly observed in the absorption spectra. The spectral positions of these bands were found to depend slightly on the particle size, which could be tuned by varying the annealing conditions. Hence, transmission electron microscopy showed the formation of spherical copper nanoparticles with diameters in the range of 3.3 to 5.6 nm. On the other hand, in the case of silver, both spherical nanoparticles with diameters in the range of 3 to 6 nm and nano-rods were obtained.
Electronic structure and bandgap of γ-Al2O3 compound using mBJ exchange potential
Authors: Yazdanmehr Mohsen , Asadabadi Saeid Jalali , Nourmohammadi Abolghasem , Ghasemzadeh Majid , Rezvanian Mahmood
Published: September 2012

γ-Al2O3 is a porous metal oxide and described as a defective spinel with some cationic vacancies. In this work, we calculate the electronic density of states and band structure for the bulk of this material. The calculations are performed within the density functional theory using the full potential augmented plan waves plus local orbital method, as embodied in the WIEN2k code. We show that the modified Becke-Johnson exchange potential, as a semi-local method, can predict the bandgap in better agreement with the experiment even compared to the accurate but much more expensive green function method. Moreover, our electronic structure analysis indicates that the character of the valence band maximum mainly originates from the p orbital of those oxygen atoms that are close to the vacancy. The charge density results show that the polarization of the oxygen electron cloud is directed toward aluminum cations, which cause Al and O atoms to be tightly connected by a strong dipole bond.
Singly ionized double-donor complex in vertically coupled quantum dots
Authors: Manjarres-García Ramón , Escorcia-Salas Gene Elizabeth , Mikhailov Ilia D , Sierra-Ortega José
Published: September 2012

The electronic states of a singly ionized on-axis double-donor complex (D
2
+) confined in two identical vertically coupled, axially symmetrical quantum dots in a threading magnetic field are calculated. The solutions of the Schrödinger equation are obtained by a variational separation of variables in the adiabatic limit. Numerical results are shown for bonding and antibonding lowest-lying artificial molecule states corresponding to different quantum dot morphologies, dimensions, separation between them, thicknesses of the wetting layers, and magnetic field strength.
Antiproliferative and cell apoptosis-inducing activities of compounds from Buddleja davidii in Mgc-803 cells
Authors: Wu Jian , Yi Wenshi , Jin Linhong , Hu Deyu , Song Baoan
Published: September 2012

Background

Buddleja davidii is widely distributed in the southwestern region of China. We have undertaken a systematic analysis of B. davidii as a Chinese traditional medicine with anticancer activity by isolating natural products for their activity against the human gastric cancer cell line Mgc-803 and the human breast cancer cell line Bcap-37.

Results

Ten compounds were extracted and isolated from B. davidii, among which colchicine was identified in B. davidii for the first time. The inhibitory activities of these compounds were investigated in Mgc-803, Bcap-37 cells in vitro by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and the results showed that luteolin and colchicine had potent inhibitory activities against the growth of Mgc-803 cells. Subsequent fluorescence staining and flow cytometry analysis indicated that these two compounds could induce apoptosis in Mgc-803 cells. The results also showed that the percentages of early apoptotic cells (Annexin V+/PI-, where PI is propidium iodide) and late apoptotic cells (Annexin V+/PI+) increased in a dose- and time-dependent manner. After 36 h of incubation with luteolin at 20 μM, the percentages of cells were approximately 15.4% in early apoptosis and 43.7% in late apoptosis; after 36 h of incubation with colchicine at 20 μM, the corresponding values were 7.7% and 35.2%, respectively.

Conclusions

Colchicine and luteolin from B. davidii have potential applications as adjuvant therapies for treating human carcinoma cells. These compounds could also induce apoptosis in tumor cells.