bluuebunny/crossref_metadata_2025 huggingface dataset:
The unidimensional self-efficacy scale for MS (USE-MS): developing a patient based and patient reported outcome
Authors: Young CA , Mills RJ , Woolmore J , Hawkins CP , Tennant A
Published: April 2012

Background:

Self-efficacy concerns the individual’s belief that he or she is capable of performing a certain task and producing a desired effect, i.e. it reflects the person’s perceptions of their capability for specific tasks, as distinct from their actual ability. Self-efficacy has been shown to influence motivation, psychological well-being, adherence with treatment regimes and quality of life in multiple sclerosis and other conditions.

Objective:

To develop a unidimensional scale of MS self-efficacy with robust psychometric properties, suitable for patient self report.

Methods:

A questionnaire pack covering three MS self-efficacy scales, the Dispositional Resilience Scale and demographic data was posted to MS patients from two MS databases. Data underwent Rasch analysis.

Results:

Response rate was 309/600 (51.5%). None of the existing MS self-efficacy scales were unidimensional. A new 12-item scale, created by combining items from our two scales, was shown to fit the Rasch model, was unidimensional, and invariant for gender, education and disease duration.

Conclusion:

The Unidimensional Self-Efficacy scale for MS (USE-MS) provides a simple summated scale for an ordinal estimate of a persons’ self efficacy. A transformation to interval scaling is available for use in the calculation of change scores and effect sizes.
Nonword repetition performance and related factors in children representing four linguistic groups
Authors: Lee Sue Ann S. , Gorman Brenda K.
Published: April 2012

The current study was designed to compare the English nonword repetition accuracy in 7-year-old monolingual English, Korean–English bilingual, Chinese–English bilingual, and Spanish–English bilingual children. The relationships among nonword repetition accuracy, vocabulary, phonological awareness, and phonotactic probability in each group of children were also examined. The results indicated significant differences among the groups’ accuracy of consonants and vowels by syllable length. Different correlational patterns emerged among nonword repetition accuracy, vocabulary, and phonological awareness. Theoretical and clinical implications for the use of nonword repetition tasks for children from various linguistic backgrounds are discussed.
Easing in: Fluent processing brings others into the ingroup
Authors: Claypool Heather M. , Housley Meghan K. , Hugenberg Kurt , Bernstein Michael J. , Mackie Diane M.
Published: April 2012

Four experiments demonstrated that perceptual fluency can facilitate categorization of others as ingroup members. In Experiment 1 (replications A, B, and C), White participants were first exposed to a group of White target individuals and later judged whether fluent (repeated) and disfluent (novel) targets were members of a particular ingroup or not. In each replication, fluent targets were categorized as ingroup members more readily than were disfluent ones. Experiment 2 replicated and extended this finding by showing that both White (racial ingroup) and Black (racial outgroup) targets were more frequently perceived as school ingroup members when fluent (repeated). In Experiments 3 and 4, fluency was manipulated via visual clarity and, again, fluency engendered more ingroup categorizations than did disfluency, for both racial ingroup and outgroup targets. Moreover, findings from Experiment 4 suggested that liking fully mediated the fluency–ingroup categorization relation. Implications of these findings for the literatures on fluency and intergroup relations are discussed.
Empowerment training and direct support professionals’ attitudes about individuals with intellectual disabilities
Authors: Flatt-Fultz Elizabeth , Phillips Lindsay A.
Published: April 2012

The purpose of this study was to determine if viewing a training video on empowerment of individuals with an intellectual and developmental disability would change the attitudes of direct support professionals (DSPs). Participants were 43 DSPs from a human service provider to individuals with intellectual and developmental disabilities. We randomly assigned them to one of two groups. A control group completed the Community Living Attitude Scale (CLAS–MR) without viewing a training video on empowerment until after CLAS–MR completion. The experimental group viewed the video on empowerment and then completed the CLAS–MR. The hypothesis was supported in that DSPs who viewed the video prior to CLAS–MR completion had significantly more empowering attitudes towards individuals with intellectual and developmental disabilities compared to the control group.
Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial
Authors: Dreger Peter , Döhner Hartmut , McClanahan Fabienne , Busch Raymonde , Ritgen Matthias , Greinix Hildegard , Fink Anna-Maria , Knauf Wolfgang , Stadler Michael , Pfreundschuh Michael , Dührsen Ulrich , Brittinger Günter , Hensel Manfred , Schetelig Johannes , Winkler Dirk , Bühler Andreas , Kneba Michael , Schmitz Norbert , Hallek Michael , Stilgenbauer Stephan
Published: April 2012

The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.
Effect of the aqueous extract of Senecio biafrae (Oliv. & Hiern) J. Moore on sexual maturation of immature female rat
Authors: Lienou Landry L , Telefo Bruno P , Bale Bayala , Yemele Didiane , Tagne Richard S , Goka Stephanie C , Lemfack Chantal M , Mouokeu Celestin , Moundipa Paul F
Published: April 2012

Background

Senecio biafrae (Asteraceae) is a medicinal plant widely used by traditional healers in the western region of Cameroon for the treatment of female infertility. This experiment was designed to evaluate the effect of the aqueous extract from leaves and stems of S. biafrae (AESb) on the onset of puberty and some biochemical and physiological parameters of reproduction in immature Wistar female rats.

Methods

Different doses of AESb were daily and orally administered to immature female rats (13 animals/group) for 30 days. At the end of the treatment period, six animal of each experimental group were sacrificed and their body, ovarian, uterus weight; uterine, ovarian protein or cholesterol level as well as data on puberty onset recorded. The remaining animals of each group were used for the fertility test and some gestational parameters recorded.

Results

A linear increase in the growth rate of all animals was observed. The body weight gain in animals treated at the dose of 8 mg/kg of AESb significantly increased (p < 0.05) after 25 days of treatment while those receiving the doses of 32 and 64 mg/kg presented a significantly low body weight gain starting from the 19th day till the end of the treatment period. The ages (days) of animals at vaginal opening (VO) was significantly reduced (p < 0.05) in those treated with the doses of 32 (41.25 ± 0.51) and 64 mg/kg (41.42 ± 0.54) as compared to control animals (43.33 ± 0.73). AESb significantly increased (p < 0.05) the ovarian weight and the number of corpora lutea in animals treated with 8 mg/kg as well as the uterine weight and protein levels irrespective of the dose. No significant effect of the extract on various fertility and gestational parameters was registered.

Conclusion

The overall results of the present study provide evidence on the puberty onset induction and ovarian folliculogenesis effect of AESb in immature female rat.
Tumourigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems
Authors: Nelson Scott A. , Li Zhouyu , Newton Ian P. , Fraser David , Milne Rachel E. , Martin David , Schiffmann David , Yang Xuesong , Dormann Dirk , Weijer Cornelis J. , Appleton Paul L. , Näthke Inke S.
Published: April 2012

Nonsense mutations that result in expression of truncated, N-terminal fragments of the APC tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumourigenesis by eliminating β-catenin binding sites from APC, which leads to upregulation of β-catenin to result in induction of oncogenes such as MYC. Here we show that in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC) results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution, three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of wild type and APC heterozygous tissue from APCMin/+ mice demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, cells expressing N-APC fail to migrate normally; amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but failed to perform directional chemotaxis; multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APCMin/+intestines are overpopulated with cells suggesting that a lack of migration may cause cell accumulation in a pre-cancerous state.
Endovenous laser ablation for major varicose tributaries
Authors: Myers K A , Clough A , Tilli H
Published: April 2012

Objective

The purpose was to determine whether endovenous laser ablation (EVLA) could be used to treat major varicose tributaries as well as saphenous veins.

Methods

From 173 major venous systems in 95 patients treated by EVLA over a 12-month period, 108 had major varicose tributaries, of which 78 (70%) were treated by attempted EVLA of the saphenous veins and associated tributaries.

Results

Treatment was successful in 71 venous segments (83%). The lengths of saphenous veins treated were 3–46 (median 18) cm. and the lengths of tributaries treated were 3–38 (median 14) cm. The diameters of treated saphenous veins were 4–10 (median 6) mm, and the estimated mean diameters of treated tributaries were 3–8 (median 5) mm, as measured prior to operation with the patient in 45° reverse Trendelenburg on a tilt table. There were no early or delayed complications.

Conclusions

Major varicose tributaries as well as the saphenous veins can be treated by EVLA in approximately two-thirds of cases, with success in the majority selected and with no significant complications.
Bilateral Sudden Sensorineural Hearing Loss and Chronic Venous Cerebrospinal Insufficiency: A Case Report
Authors: Alpini D , Bavera P M , Di Berardino F , Barozzi S , Cesarani A
Published: April 2012

Objectives:

We report a case of bilateral sudden sensorineural hearing loss (SSHL) in a patient suffering from chronic venous cerebrospinal insufficiency (CCSVI).

Methods:

Audiometric testing confirmed bilateral sensorineural hearing loss with hypoexcitability to caloric stimulation on the left side and echo-colour Doppler examination showed abnormal cerebral venous deficiency.

Results:

The patient's condition improved after 15 days following medical treatment.

Conclusions:

CCSVI may explain the anatomical background which provides a predisposing factor for SSHL although further studies are needed to verify whether this observation is casual or coincidental.
Managing Inventory in Global Supply Chains Facing Port-of-Entry Disruption Risks
Authors: Lewis Brian M. , Erera Alan L. , Nowak Maciek A. , Chelsea C. White
Published: April 2012

Ports-of-entry are critical components of the modern international supply chain infrastructure, particularly container seaports and airfreight hubs. The potential operational and economic impact resulting from their temporary closure is unknown but is widely believed to be very significant. This paper investigates one aspect of this potential impact, focusing specifically on the use of supply chain inventory as a risk mitigation strategy for a one supplier, one customer system in which goods are transported through a port-of-entry subject to temporary closures. Closure likelihood and duration are modeled using a completely observed, exogenous Markov chain. Order lead times are dependent on the status of the port-of-entry, including potential congestion backlogs of unprocessed work. An infinite-horizon, periodic-review inventory control model is developed to determine the optimal average cost ordering policies under linear ordering costs with backlogged demand. When congestion is negligible, the optimal policy is state invariant. In the more complex case of nonnegligible congestion, this result no longer holds. For studied scenarios, numerical results indicate that operating margins may decrease 10% for reasonable-length port-of-entry closures, that margins may be eliminated completely without contingency plans, and that expected holding and penalty costs may increase 20% for anticipated increases in port-of-entry utilization.
Securitizing Environmental Risk and the Keystone XL Pipeline
Authors: Smith Kerry
Published: April 2012

When faced with irreversible decisions with significant uncertainty about the environmental costs of accidents, such as the Keystone XL Pipeline or hydro-fracking for natural gas, policymakers should use an environmental bond to securitize self insurance.
Mobile Laboratory Unit: a disruptor solution for hemostasis management during major surgery. Usage in the context of face transplantation
Authors: Leon-Justel Antonio , Noval-Padillo Jose Angel , Polonio Franciso , Gomez-Cia Tomas , Hinojosa Rafael , Porras Manuel , De-Blas Jose M. , Solomon Cristina , Guerrero Juan M.
Published: April 2012

The management of surgical bleeding during a face transplant in a patient diagnosed with bilateral neurofibromatosis is quite complex. With the actual methods and technology for hemostasis management, it may not always be possible to give the clinician the support needed to manage operative associated bleeding. Bedside hemostasis monitors are needed urgently to assist clinicians in making the correct diagnosis in a timely manner.

Our Mobile Laboratory Unit is a disruptive solution for hemostasis management during major surgery as it allows real-time monitoring, the predominant mechanism of bleeding and goal-direct coagulation therapy. The unit is an autonomous mobile platform that can be moved immediately to anywhere its service is needed and offers a complete flexible laboratory test which includes biochemistry, hematology and coagulation studies as standard equipment.

In our case the test performed by the unit allowed us to identify the reason for our patient’s bleeding at the bedside. Severely decreased clot firmness of the fibrin-based clot and a less impaired firmness of the whole blood clot, suggested an acceptable contribution of platelets to the clot quality, but decreased polymerization of fibrinogen into fibrin.

In our opinion new insights into the pathophysiology of coagulopathy, the availability of technology such as our Mobile Laboratory Unit, and awareness of side effects of intravenous fluids should encourage the idea that perhaps it is time to change hemostasis management in operation-related bleeding.
Blood presence of circulating oncofetal fibronectin mRNA, by RT-PCR, does not represent a useful specific marker for the management and follow-up of thyroid cancer patients
Authors: Vendittelli Francesca , Raffaelli Marco , Fadda Guido , Carelli-Alinovi Cristiana , Paolillo Carmela , Bellantone Rocco , Zuppi Cecilia , Capoluongo Ettore
Published: April 2012

Recent studies strongly suggest the use of oncofetal fibronectin (onfFN) mRNA in diagnostic follow-up and staging due to its very high specificity for thyroid cancers. Since the use of this marker has not been well established yet, particularly in the monitoring of minimal residual disease, we have tried to verify the diagnostic power of onfFN and its usefulness as a prognostic molecular marker. For this reason, we evaluated (by RT-PCR) the presence of onfFN mRNAs, not only in blood samples and thyroid tissues (both normal and neoplastic), but also in different biological fluids (such as K

Molecular investigations, such as RT-PCR protocol, and sequencing of onfFN cDNAs evaluation of the above-mentioned samples were performed.

The onfFN transcript was largely expressed in all benign and malignant thyroid tissues [differentiated thyroid carcinomas (DTCs)] tested as well as in a large number of biological fluids; in particular, 100% urine samples were positive for onfFN transcript as compared to the thyroglobulin (Tg) mRNA (75%), while saliva was always positive for onfFN and never for Tg. These findings indicate that onfFN cannot be considered a marker specific for thyroid cancer presence. Finally, Tg results were positive in a large part of the samples, but not always in concomitance with onfFN.

We underline how the complexity of onfFN transcripts could affect the RT-PCR procedure. In addition, the presence of onfFN transcripts in several normal and cancer tissues, along with non-thyroid biological fluids or cells, does not allow the use of this marker for cancer monitoring.
Quantification of human serum insulin concentrations in clinical pharmacokinetic or bioequivalence studies: what defines the “best method”?
Authors: Cassidy James P. , Luzio Stephen D. , Marino Mark T. , Baughman Robert A.
Published: April 2012

Historically, quantitative clinical diagnostic assays (QCDAs) have not been accepted for use in pharmacokinetic or bioequivalence studies because they do not fully comply with the US Food and Drug Administration (FDA) Guidance for Industry: Bioanalytical Method Validation (e.g., full calibration curve not generated with each analytical run). Samples from a bioequivalence study were analysed for insulin and C-peptide concentrations with QCDAs and guidance-conforming radioimmunoassays (RIAs) and the results compared across and within assays.

Serum samples (n=1913) from study MKC-TI-142 were analysed first using the Roche E170 electrochemiluminescence immunoassay (ECLIA) for insulin concentration and the Immulite 2000 chemiluminescence immunoassay (CLIA) for C-peptide, and then using the corresponding Millipore RIAs.

The insulin assays were highly correlated: r

The science indicates that the QCDAs are appropriate for the quantification of serum insulin (ECLIA) and C-peptide (CLIA) concentrations in human pharmacokinetic and bioequivalence studies even though the calibration curve is not generated in each analytical run.
A comprehensive review of upper reference limits reported for (high-)sensitivity cardiac troponin assays: the challenges that lie ahead
Authors: Cardinaels Eline P.M. , Mingels Alma M.A. , Jacobs Leo H.J. , Meex Steven J.R. , Bekers Otto , van Dieijen-Visser Marja P.
Published: April 2012

Cardiac troponins (cTn) are the preferred markers for the diagnosis of acute myocardial infarction (AMI). The guidelines recommend the use of the 99th percentile upper reference concentration of a healthy population as the diagnostic cut-off for AMI. However, a broad range of upper reference limits is still employed, complicating the diagnosis of AMI. This overview is meant to assist laboratory specialists to define an appropriate cut-off value for the diagnosis of AMI. Therefore, we provide an overview of the analytical performance and upper reference limits of seven (high-)sensitivity cTn assays: Roche high-sensitivity cTnT and ADVIA Centaur, Stratus CS, Dimension Vista, Vitros ECi, Access and Architect cTnI assays. It is shown that none of the reference populations completely met the guidelines, including those in package inserts. Forty percent of the studies collected less than the advised minimum of 300 subjects. Many studies (50%) did not report their inclusion criteria, while lower 99th percentile limits were observed when more stringent selection criteria were applied. Higher troponin cut-offs were found in men and elderly subjects, suggesting sex- and age-specific cut-offs would be considered. Therefore, there is still need for a large, rigorously screened reference population to more accurately establish cTn upper reference limits.
The performance of high sensitivity troponin for the diagnosis of acute myocardial infarction is underestimated
Authors: Aldous Sally J. , Florkowski Chris M. , Crozier Ian G. , Than Martin P.
Published: April 2012

Many papers evaluating high sensitivity troponin assays make the diagnosis of myocardial infarction based on conventional troponin assays in clinical use at the time of recruitment. Such analyses often do not show superiority of high sensitivity assays compared with contemporary assays meeting precision guidelines.

Three hundred and twenty-two patients presenting to the emergency department between November 2006 and April 2007 for evaluation for acute coronary syndrome had serial (0 h and >6 h) bloods taken to compare troponin assays (Roche hsTnT, Abbott TnI, Roche TnT and Vitros TnI). The diagnosis of myocardial infarction was made using each troponin assay separately with which that same assay was analysed for diagnostic performance.

The rate of myocardial infarction would be 38.9% using serial hsTnT, 31.3% using serial Abbott TnI, 27.1% using serial TnT and 26.4% using serial Vitros TnI. The baseline sensitivities (0 h) are 89.9% (85.2–93.3) for hsTnT, 77.9% (71.0–87.5) for Abbott TnI, 73.0% (65.6–78.7) for TnT and 86.8% (74.6–94.4%) for Vitros TnI. The specificities (peak 0 h and >6 h samples) are 93.1% (91.2–93.1) for hsTnT, 88.3% (86.5–88.3) for Abbott TnI, 92.2% (90.5–92.2) for TnT and 90.6% (70.1–90.6) for Vitros TnI.

hsTnT has superior sensitivity for myocardial infarction than even assays at or near guideline precision requirements (Abbott and Vitros TnI). The specificity of hsTnT assay is not as poor as previous analyses suggest.
Measurement of high-molecular-weight adiponectin is not useful in assessing coronary stenosis
Authors: Imatoh Takuya , Miyazaki Motonobu , Kadowaki Ken , Tanihara Shinichi , Akashi Chinami , Une Hiroshi
Published: April 2012

In many studies, high-molecular-weight (HMW) adiponectin has been considered the active form of adiponectin. However, whether HMW adiponectin is a good surrogate marker for coronary artery disease still needs to be elucidated.

We conducted a hospital-based cross-sectional study to examine the relationship between total, HMW or non-HMW adiponectin concentrations and coronary stenosis in 83 male patients and 138 male controls.

Patients with coronary stenosis had significantly lower total adiponectin concentrations compared with controls. Non-HMW adiponectin concentrations in cases were significantly lower than the controls. However, there were no significant differences between cases and controls in HMW adiponectin concentrations. From the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for total and non-HMW adiponectin was significantly larger than that for HMW adiponectin concentrations. Of the three models, that for non-HMW adiponectin showed the largest AUC (total adiponectin 0.74, HMW adiponectin 0.54, and non-HMW adiponectin 0.79).

Despite associations between total adiponectin levels and coronary stenosis, our data go against any apparent association between HMW adiponectin concentrations and coronary stenosis.
Detection of α-globin gene deletion and duplication using quantitative multiplex PCR of short fluorescent fragments
Authors: Mo Zong-Ping , Yu Chang-Shun , Li Ya-Juan , Cao Wei-xi , Zeng Zheng-Yu , Zhan Yi-Xin , Mo Gui-ling , Hu Chaohui , Feng Wenli
Published: April 2012

The aim of this study was to establish a sensitive method that can detect the presence of not only the common but also the unusual or unknown α-globin gene deletions for screening of α-thalassemia. We used quantitative multiplex PCR of short fluorescent fragments (QMPSF) for the α-globin genes (

We set up and validated HBA-QMPSF using 50 negative and 100 positive controls of deletional α-thalassemia. To evaluate its ability to detect the presence of the common and unusual or unknown α-globin gene deletions, 579 unrelated samples were simultaneously analyzed using this assay and multiplex Gap polymerase chain reaction (Gap-PCR). The inconsistent results were further confirmed by multiplex ligation-dependent probe amplification (MLPA).

HBA-QMPSF was capable of detecting α-globin gene deletions with an acceptable variability as shown by mean values (SD) of allele dosage for the heterozygous deleted control obtained from intra- and inter-experimental replicates [0.63 (0.01) and 0.61 (0.03)]. In 572 out of the 579 unrelated subjects, HBA-QMPSF and multiplex Gap-PCR gave consistent results. In seven cases which were finally proved to be composed of one rare deletion --

HBA-QMPSF is able to detect the presence of the common and unusual or unknown α-thalassemia deletions and duplications. It can be used as an initial screening test for α-thalassemia caused by
A sensitive quantitative test strip based point-of-care albuminuria screening assay
Authors: Decavele An-Sofie C. , Fiers Tom , Penders Joris , Delanghe Joris R.
Published: April 2012

Chronic kidney disease is a major health problem and the global guidelines require screening of albuminuria. Therefore, affordable and sensitive albuminuria screening tests are needed. We explored the potential of urine strips, generally reported in the ordinal scale, measured on an automatic strip reader for reporting quantitative and sensitive albumin results.

We compared reflectance data of Combur-Test

Imprecision of the reflectance signal of the Cobas U411 was measured with commercial control material (Bio-Rad). Inter-run coefficients of variations (CVs) for reflectance for levels 1 and 2 were 1.7%/4.9%, respectively, and intra-run CVs were 1.8%/4.2%, respectively. Good agreement was obtained between the albumin concentration of the BNII and the protein strip reflectance data (n=389): Y (10000/protein reflectance, 1/%)=160+0.132·X (albuminuria BNII, mg/L)–0.0000111·X

The present study demonstrates that reflectance data generated by a test strip reader allows for quantitative analysis of albumin. Although the lower limit of the microalbumin range (30 mg/L) cannot be achieved with the dye-binding method, the results are satisfactory for screening purposes.
The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer
Authors: White Nicole M.A. , Youssef Youssef M. , Fendler Annika , Stephan Carsten , Jung Klaus , Yousef George M.
Published: April 2012

Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We compiled a comprehensive list of 55 miRNAs that are differentially expressed in PCa from previous microarray analysis and published literature. Target prediction analyses showed that 29 of these miRNAs are predicted to target 10 KLKs. Eight of these miRNAs were predicted to target more than one KLK. Quantitative real-time (qRT)-PCR demonstrated that there was an inverse correlation pattern in the expression (normal vs. cancer) between dysregulated miRNAs and their target KLKs. In addition, we experientially validated the miRNA-KLK interaction by transfecting miR-331-3p and miR-143 into a PCa cell line. Decreased expression of targets KLK4 and KLK10, respectively, and decreased cellular growth were observed. In addition to KLKs, dysregulated miRNAs were predicted to target other genes involved in the pathogenesis of PCa. These data show that miRNAs can contribute to KLK regulation in PCa. The miRNA-KLK axis of interaction projects a new element in the pathogenesis of PCa that may have therapeutic implications.
Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance
Authors: Avgeris Margaritis , Mavridis Konstantinos , Scorilas Andreas
Published: April 2012

Tissue kallikrein (KLK1) and kallikrein-related peptidases (KLK2–15) comprise a family of 15 highly conserved secreted serine proteases with similar structural characteristics and a wide spectrum of functional properties. Both gene expression and protein activity of KLKs are rigorously controlled at various levels via diverse mechanisms, including extensive steroid hormone regulation, to exert their broad physiological role. Nevertheless, deregulated expression, secretion, and function of KLK family members has been observed in several pathological conditions and, particularly, in endocrine-related human malignancies, including those of the prostate, breast, and ovary. The cancer-related abnormal activity of KLKs upon substrates such as growth factors, cell adhesion molecules, cell surface receptors, and extracellular matrix proteins facilitate both tumorigenesis and disease progression to the advanced stages. The well-documented relationship between KLK status and the clinical outcome of cancer patients has led to their identification as promising diagnostic, prognostic, and treatment response monitoring biomarkers for these complex disease entities. The main objective of this review is to summarize the existing knowledge concerning the role of KLKs in prostate, breast, and ovarian cancers and to highlight their continually evolving biomarker capabilities that can provide significant benefits for the management of cancer patients.
High-speed rail modal split on routes with high air traffic density
Authors: López Pita Andrés , Teixeira Paulo Fonseca , Ferreira Patrícia Afonso
Published: April 2012

The impact of high-speed railways on routes with high air traffic density was investigated and analysed. The case considered was the Madrid–Barcelona route, which had the highest volume of air traffic in Europe, nearly 5 million passengers per year, prior to the opening of the high-speed railway line in February 2008. Demand and market share evolution is evaluated and a comparison is made with other cases and with the forecasts presented in a previous paper. The results show that, as forecast, with maximum speeds of 300 km/h, the high-speed market share in routes where air competition is very strong does not reach the levels usually obtained in previous European high-speed links where competition from air transport was less important.
Sampling strategy for pavement distress survey: a case study
Authors: Rajbongshi Pabitra , Kachru Kunal , Das Animesh
Published: April 2012

Before taking up a detailed structural evaluation of pavements, a reconnaissance survey of the pavement surface distresses is usually employed. For an entire road network such a survey involves considerable cost and time. This paper attempts to focus on the sampling strategy for distress survey where the survey can be conducted for the partial length of a given road. The fatigue cracking on an asphalt pavement was chosen as surface distress for the present case study. A videographic survey was conducted on some local in-service asphalt pavement sections. From the analysis of data collected in the present study, it was observed that the distribution of fatigue cracking with a mean value less than approximately 20% followed an exponential distribution. It was also seen that the sample mean distress level was within ±10% of the population mean, if only 20% of road length was surveyed.
Lateral resistance of railway track with frictional sleepers
Authors: Zakeri Jabbar-Ali , Mirfattahi Behrouz , Fakhari Maryam
Published: April 2012

The welding of rail joints on sharp curves is not practicable due to the lack of sufficient lateral resistance of the railway track. Consequently, maintenance costs increase rapidly for many old railway tracks. Moreover, deterioration of the track components, plastic deformation and critical cracks in the rail head, failures in sleepers and fasteners, ballast bed damage and lateral movement of railway track occur in the rail joints. As the resistance of a sleeper to lateral displacement in a ballast bed mainly consists of the frictional forces between the ballast particles and the sleeper bottom, the present study investigated the changes in resistance of railway tracks to lateral displacement using the single sleeper push test on the frictional concrete sleeper (B70-F). The results were then compared with those for the standard sleeper, B70. An experiment was conducted on a track with and without frictional sleepers and its result showed that the lateral resistance of the railway track increased by 64% by using frictional sleepers. In addition, a field investigation was conducted on an actual track with and without B70-F sleepers in order to extend the results and the conclusion was that the resistance of the railway track to lateral displacement increased by approximately 68% when using B70-F sleepers.
Long-Term Renal and Cardiovascular Outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants by Baseline Estimated GFR
Authors: Rahman Mahboob , Ford Charles E. , Cutler Jeffrey A. , Davis Barry R. , Piller Linda B. , Whelton Paul K. , Wright Jackson T. , Barzilay Joshua I. , Brown Clinton D. , Colon Pedro J. , Fine Lawrence J. , Grimm Richard H. , Gupta Alok K. , Baimbridge Charles , Haywood L. Julian , Henriquez Mario A. , Ilamaythi Ekambaram , Oparil Suzanne , Preston Richard
Published: April 2012

Background and objectives

CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone.

Design, setting, participants, & measurements

This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4–8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m2) as follows: normal/increased (≥90; n=8027), mild reduction (60–89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD.

Results

After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD.

Conclusions

CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.
Having Fun in the Thaw: Youth Initiative Clubs in the Post-Stalin Years
Authors: Tsipursky Gleb
Published: April 2012

This essay explores a novel cultural institution of the Thaw, youth initiative clubs. Created in 1956, these clubs offered young people an opportunity to take a leading role in organizing and managing cultural activities at the grassroots level. These new organizations emblematized what the author argues represented a major shift by the Thaw-era authorities to inspiring youth initiative from below as a means of forging a post-Stalinist model of young citizens characterized by enthusiasm and autonomy and thus seen as capable of taking charge over building communism. At the same time, the Soviet leadership intended youth initiative clubs to increase social control by getting young people into official cultural collectives. A close investigation of the youth initiative club movement reveals that these diverse goals bred some tensions at the ground level. Young club activists, empowered by top-level calls for popular initiative, struggled to overcome the opposition of certain entrenched bureaucrats who refused to discard the Stalinist emphasis on obedience and discipline. In other cases, club members pursued activities that departed from the intentions of the Kremlin itself. Nonetheless, the essay finds that many young people found friends, emotional support, a source of meaning, and a great deal of fun within youth initiative clubs. The author therefore shows that official Soviet collectives were not invariably repressive institutions that minimized individual autonomy, but could instead provide significant opportunities for popular agency, grassroots organization, and pleasurable entertainment, illustrating concordances between the Soviet population and the government.
Nietzsche on Agency and Self-Ignorance
Authors: Paul Katsafanas
Published: April 2012

Nietzsche frequently claims that agents are in some sense ignorant of their own actions. But what exactly does Nietzsche mean by this claim, and how would the truth of this claim affect philosophical models of agency? I argue that Nietzsche intends to draw attention to the fact that there are influences on reflective episodes of choice that have three features. First, these influences are pervasive, occurring in every episode of choice. Second, these influences are normatively significant, in that their presence typically affects the outcome of deliberation. Third, these influences are difficult to detect, in that one needs to acquire a great deal of self-knowledge in order to begin to counteract their effects. I briefly sketch the way in which these claims follow from Nietzsche's philosophical psychology.
Suffering and the Affirmation of Life
Authors: Clark Maudemarie
Published: April 2012

Bernard Reginster's book The Affirmation of Life (2006) purports to fill a gap in our understanding of Nietzsche's philosophical project by explaining why Nietzsche regards the affirmation of life as his defining philosophical achievement. Reginster is not alone in emphasizing the centrality of life affirmation to Nietzsche's thought. What makes Reginster's book new and original is his systematic approach—his attempt to isolate a core of Nietzsche's philosophy and show how everything else, especially the affirmation of life, is related to it. This article challenges the systematicity Reginster finds in Nietzsche's work; above all, it rejects Reginster's claim that what has led to nihilism is the condemnation of suffering, a view Nietzsche is said to inherit from Schopenhauer. I raise questions about how much of Schopenhauer's view Nietzsche in fact retains and about how well Reginster's account of affirmation fits with Nietzsche's account of the will to power, which, as I have argued elsewhere, has played an essential part in producing all the things Nietzsche values.
Metaethics and Nihilism in Reginster's The Affirmation of Life
Authors: J. Z. Hussain Nadeem
Published: April 2012

Bernard Reginster, in his book The Affirmation of Life: Nietzsche on Overcoming Nihilism, takes up the challenge of figuring out what Nietzsche might mean by nihilism and the revaluation of values. He argues that there is an alternative, normative subjectivist interpretation of Nietzsche's views on nihilism and revaluation that makes as much sense as—indeed, he often clearly leans toward thinking that it makes more sense than—a fictionalist reading of Nietzsche. I argue that his arguments do not succeed. Once we have looked carefully at the details of the positions and the arguments ascribed to Nietzsche, the fictionalist option is the more charitable interpretation of the texts. I focus on the metaethical issues that play a central role for Reginster in his articulation of Nietzsche's nihilism and Nietzsche's strategy for overcoming nihilism.
Latent Futures of Iranian Architecture
Authors: Hensel Michael
Published: April 2012

How is it possible to draw on inherited technical and cultural knowledge while being projective and anticipating an evolving future? Michael Hensel highlights the value of recognising essential Iranian sensibilities and identifying salient past traits that can be redeveloped into an enlightened contemporary approach. What sort of novel amalgamations might point towards the most promising futures for Iranian architectural design?
Brief Report: Candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity
Authors: Koumakis Eugénie , Giraud Matthieu , Dieudé Philippe , Cohignac Vanessa , Cuomo Giovanna , Airò Paolo , Hachulla Eric , Matucci‐Cerinic Marco , Diot Elizabeth , Caramaschi Paola , Mouthon Luc , Riccieri Valeria , Cracowski Jean‐Luc , Tiev Kiet Phong , Francès Camille , Amoura Zahir , Sibilia Jean , Cosnes Anne , Carpentier Patrick , Valentini Gabriele , Manetti Mirko , Guiducci Serena , Meyer Olivier , Kahan André , Boileau Catherine , Chiocchia Gilles , Allanore Yannick
Published: April 2012

Objective

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) share some pathophysiologic bases as evidenced by individual and familial polyautoimmunity and common susceptibility genetic factors. With regard to the latter, there has been a recent shift from the “common variant” to the “rare variant” paradigm, since rare variants of TNFAIP3 and TREX1 with large effect sizes have recently been discovered in SLE. The present study was undertaken to investigate whether rare variants of TNFAIP3 and TREX1 are also associated with SSc.

Methods

TREX1 single‐nucleotide polymorphisms (SNPs) rs3135946, rs7626978, rs3135943, and rs11797 and TNFAIP3 SNPs rs9494883, rs72063345, rs5029939, rs2230926, rs117480515, and rs7749323 were genotyped in a discovery set (985 SSc patients and 1,011 controls), and replication analysis of the most relevant results was performed in a second set (622 SSc patients and 493 controls).

Results

No association between TREX1 variants and SSc was observed. For TNFAIP3, we first demonstrated that a low‐frequency variant, rs117480515, tagged the recently identified TT>A SLE dinucleotide. In the discovery sample, we observed that all tested TNFAIP3 variants were in linkage disequilibrium and were associated with SSc and various SSc subsets, including the polyautoimmune phenotype. We subsequently genotyped rs117480515 in the replication sample and found it to be associated solely with the SSc polyautoimmune subset (odds ratio 3.51 [95% confidence interval 2.28–5.41], P = 8.58 × 10−9) in the combined populations. Genotype–messenger RNA (mRNA) expression correlation analysis revealed that the TNFAIP3 rs117480515 risk allele was associated with decreased mRNA expression.

Conclusion

The present findings establish the TNFAIP3 locus as a susceptibility factor for the subset of SSc with a polyautoimmune phenotype. Our results support the implication of rare/low‐frequency functional variants and the critical role of A20 in autoimmunity.
The conundrum of sharing research data
Authors: Borgman Christine L.
Published: April 2012

We must all accept that science is data and that data are science, and thus provide for, and justify the need for the support of, much‐improved data curation. (Hanson, Sugden, & Alberts, )

Researchers are producing an unprecedented deluge of data by using new methods and instrumentation. Others may wish to mine these data for new discoveries and innovations. However, research data are not readily available as sharing is common in only a few fields such as astronomy and genomics. Data sharing practices in other fields vary widely. Moreover, research data take many forms, are handled in many ways, using many approaches, and often are difficult to interpret once removed from their initial context. Data sharing is thus a conundrum. Four rationales for sharing data are examined, drawing examples from the sciences, social sciences, and humanities: (1) to reproduce or to verify research, (2) to make results of publicly funded research available to the public, (3) to enable others to ask new questions of extant data, and (4) to advance the state of research and innovation. These rationales differ by the arguments for sharing, by beneficiaries, and by the motivations and incentives of the many stakeholders involved. The challenges are to understand which data might be shared, by whom, with whom, under what conditions, why, and to what effects. Answers will inform data policy and practice.
Shaping the niche: Lessons from the Drosophila testis and other model systems
Authors: Papagiannouli Fani , Lohmann Ingrid
Published: April 2012

Stem cells are fascinating, as they supply the cells that construct our adult bodies and replenish, as we age, worn out, damaged, and diseased tissues. Stem cell regulation relies on intrinsic signals but also on inputs emanating from the neighbouring niche. The Drosophila testis provides an excellent system for studying such processes. Although recent advances have uncovered several signalling, cytoskeletal and other factors affecting niche homeostasis and testis differentiation, many aspects of niche regulation and maintenance remain unsolved. In this review, we discuss aspects of niche establishment and integrity not yet fully understood and we compare it to the current knowledge in other model systems such as vertebrates and plants. We also address specific questions on stem cell maintenance and niche regulation in the Drosophila testis under the control of Hox genes. Finally, we provide insights on the striking functional conservation of homologous genes in plants and animals and their respective stem cell niches. Elucidating conserved mechanisms of stem cell control in both lineages could reveal the importance underlying this conservation and justify the evolutionary pressure to adapt homologous molecules for performing the same task.
ChemInform Abstract: Investigation of Heterodimeric and Homodimeric Radical Cations of the Series: [F2O2]+, [F2Cl2]+, [Cl2O2]+, [F4]+, and [Cl4]+.
Authors: Schloeder Tobias , Riedel Sebastian
Published: April 2012

Structures, thermochemical stability, Born‐Fajans‐Haber cycles, and vibrational data of the title ions are quantum‐chemically obtained by coupled‐cluster calculations with single and double substitution as well as perturbative triple excitations.