bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active Support: A Systematic Review and Evidence-Based Practice Evaluation
Authors: Hamelin Jeffery P. , Sturmey Peter 
Published: June 2011

Abstract
Researchers have evaluated active support in agencies for persons with developmental disabilities to increase staff assistance and service user engagement. A systematic review identified two studies in which researchers reported three experimental evaluations of active support. Only one experiment showed a clear functional relationship between active support with “ineffective” to “questionable” percentage of nonoverlapping data points effect sizes and acceptable percentage of all nonoverlapping data points effect sizes. Two experiments did not show experimental control; however, there was evidence that the investigators in these studies did not sufficiently manipulate the independent variable. Based on these data, active support only meets Chambless and Hollon's (1998) criterion for a “promising treatment” but not an evidence-based practice. Future research on active support should demonstrate that the experimenter manipulated the independent variable and reported data on individual participants.
Simultaneous Phenotyping and Quantification of α-1-Antitrypsin by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Chen Yuhong , Snyder Melissa R , Zhu Yi , Tostrud Linda J , Benson Linda M , Katzmann Jerry A , Bergen H Robert 
Published: June 2011

BACKGROUNDα-1-Antitrypsin (A1AT) deficiency results from a genetic disorder at 2 common loci. Diagnosis requires quantification of A1AT and subsequent identification of the specific variant. The current algorithm of laboratory testing for the diagnosis of A1AT deficiency uses a combination of quantification (nephelometry), genotyping, and/or phenotyping. We developed a multiple reaction monitoring liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of A1AT and identification of the 2 most common deficiency alleles present in 95% of the patients with A1AT deficiency.METHODSSerum samples (n = 40) were digested with trypsin, and appropriate 13C/15N-labeled standard peptides were added. We performed LC-MS/MS analysis with a 0.5- by 150-mm C18 column and H2O:acetonitrile:n-propanol:formic acid (A:98:1:1:0.2 and B:10:80:10:0.2; flow 12 μL/min) mobile phase in positive ion mode on a TSQ Quantum triple quadrupole MS system. We measured the A1AT concentration by comparison to a calibration curve and determined the phenotype by the presence or absence of variant peptides. We compared the results to the current phenotyping assay by isoelectric focusing (IEF) and the immunonephelometry quantitative assay.RESULTSFor A1AT allele detection, in 39 of 40 samples the LC-MS/MS results were identical to those obtained by IEF gel electrophoresis. The single discrepant result was rerun by IEF at a lower dilution, and the results were in concordance. The A1AT quantification by LC-MS/MS also compared favorably with nephelometry.CONCLUSIONSThe LC-MS/MS method correlates well with current phenotyping and nephelometric assays and has the potential to improve the laboratory diagnosis of genetic A1AT deficiency.
A review of validated youth prevention and positive youth development programs in Asia
Authors: Shek Daniel T.L. , Yu Lu 
Published: June 2011

Abstract
In view of the intensification of adolescent developmental issues in different Asian contexts, there is an urgent need for developing prevention and positive youth development programs in different Asian communities. In this paper, adolescent prevention and positive youth development programs in Asia which have been evaluated by studies adopting true experimental or quasi-experimental designs are reviewed. Several observations are highlighted from this review. First, compared with Western societies, the number of validated programs in different Asian communities was extremely low. Second, there were comparatively more programs addressing substance abuse than other mental health problems. Third, compared with evaluated prevention programs, there were very few positive youth development programs. Finally, there were very few rigorously designed evaluative studies of prevention and positive youth development programs over a long period of time.
Psychopharmacological treatment of ADHD symptoms in children with autism spectrum disorder
Authors: Handen Benjamin L. , Taylor Johanna , Tumuluru Rameshwari 
Published: June 2011

Abstract
One of the most frequently reported behavioral concerns among children with autism spectrum disorder (ASD) is high rates of activity and inattention, symptoms that are often associated with attention deficit hyperactivity disorder (ADHD). Although there is a considerable body of research regarding the appropriate treatment of ADHD symptoms among typically developing children, the research among children with ASD is more limited. The evidence to date suggests that medication response rates among children with ASD are considerably lower than among typically developing children and that children with ASD tend to be at greater risk for experiencing side effects. The purpose of the present paper is to review the available research on the treatment of ADHD symptoms in children with ASD. This paper summarizes the data on a range of pharmacological options and provides specific recommendations for how best to clinically manage these symptoms.
The role of brain-derived neurotrophic factor in the pathophysiology of adolescent suicidal behavior
Authors: Sher Leo 
Published: June 2011

AbstractAdolescent suicide research has mostly focused on demographic risk factors. Such studies focus on who is at risk, but do not explain why certain adolescents are at risk for suicide. Studies of the neurobiology of adolescent suicide could clarify why some youths are more suicidal than others and help to find biological markers of suicidal behavior in teenagers. Over the past decade the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior has attracted significant attention of scientists. BDNF is involved in the pathophysiology of many psychiatric disorders associated with suicidal behavior including depression, post-traumatic stress disorder, schizophrenia, and obsessive-compulsive disorder. BDNF dysregulation could be associated with increased suicidality independently of psychiatric diagnoses. BDNF plays an important role in the regulation and growth of neurons during childhood and adolescence. Prominent among the brain regions undergoing developmental change during adolescence are stressor-sensitive areas. The serotonin dysfunction found in adolescent and adult suicidal behavior could be related to the low level of BDNF, which impedes the normal development of serotonin neurons during brain development. BDNF dysfunction could play a more significant role in the pathophysiology of psychiatric disorders and suicidal behavior in adolescents than in adults. Treatment-induced enhancement in the BDNF function could reduce suicidal behavior secondary to the improvement in psychiatric pathology or independently of improvement in psychiatric disorders. It is interesting to hypothesize that BDNF could be a biological marker of suicidal behavior in adolescents or in certain adolescent populations.
Part 2: Pharmacogenetic Variability in Drug Transport and Phase I Anticancer Drug Metabolism
Authors: Deenen Maarten J. , Cats Annemieke , Beijnen Jos H. , Schellens Jan H.M. 
Published: June 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: List currently identified candidate genes involved in phase I metabolism that are potential pharmacogenetic markers in anticancer therapy.Describe the general effect on standard treatment of allelic variants of the candidate genes and the implications for individualized treatment.
This article is available for continuing medical education credit at CME.TheOncologist.com
Equivalent drug doses in anticancer chemotherapy may lead to wide interpatient variability in drug response reflected by differences in treatment response or in severity of adverse drug reactions. Differences in the pharmacokinetic (PK) and pharmacodynamic (PD) behavior of a drug contribute to variation in treatment outcome among patients. An important factor responsible for this variability is genetic polymorphism in genes that are involved in PK/PD processes, including drug transporters, phase I and II metabolizing enzymes, and drug targets, and other genes that interfere with drug response. In order to achieve personalized pharmacotherapy, drug dosing and treatment selection based on genotype might help to increase treatment efficacy while reducing unnecessary toxicity.
We present a series of four reviews about pharmacogenetic variability in anticancer drug treatment. This is the second review in the series and is focused on genetic variability in genes encoding drug transporters (ABCB1 and ABCG2) and phase I drug-metabolizing enzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, DPYD, CDA and BLMH) and their associations with anticancer drug treatment outcome. Based on the literature reviewed, opportunities for patient-tailored anticancer therapy are presented.
Utility of mTOR Inhibition in Hematologic Malignancies
Authors: Younes Anas , Samad Nousheen 
Published: June 2011

AbstractThe mammalian target of rapamycin (mTOR) is an intracellular serine/threonine kinase that exists as a downstream component of numerous signaling pathways. The activation of mTOR results in the production of proteins involved in cell metabolism, growth, proliferation, and angiogenesis. Aberrant activation of mTOR signaling has been identified in a number of cancers, and targeted inhibition of mTOR has been successful in achieving tumor responses, prolonging progression-free survival, and increasing overall survival in various oncologic patient populations. In particular, persistent activation of mTOR signaling has been identified in cell lines and patient samples with leukemias, Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), and Waldenström's macroglobulinemia (WM). In vitro and preclinical studies using agents that inhibit mTOR signaling have demonstrated cytostatic and cytotoxic effects in these hematologic malignancies, suggesting that mTOR is a rational target for therapy in these disease states. In addition, the combination of mTOR inhibitors with traditional therapies may help to overcome the development of resistance and may improve response rates over those seen with established regimens through synergistic or additive effects. Inhibitors of mTOR signaling currently are being investigated in clinical trials of hematologic malignancies as single agents and as components of combination regimens. Thus far, promising results have been seen with the application of mTOR inhibitors as single agents in patients with relapsed or refractory leukemia, HL, NHL, MM, and WM.
Early Clinical Development of ARQ 197, a Selective, Non–ATP-Competitive Inhibitor Targeting MET Tyrosine Kinase for the Treatment of Advanced Cancers
Authors: Adjei Alex A. , Schwartz Brian , Garmey Edward 
Published: June 2011

Abstract
Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) in many cancers, and its participation in multiple signal transduction pathways involved in malignant tumor growth, suggest a wide therapeutic potential for MET inhibition in human cancer. Here we describe the discovery and early clinical development of ARQ 197, a novel, selective, non–ATP-competitive inhibitor of MET. Phase I studies demonstrate that ARQ 197 has a predictable pharmacokinetics and favorable safety profile, making it a potentially ideal partner for combination with cytotoxic chemotherapies and targeted anticancer agents. Results from phase I and phase II trials demonstrate preliminary evidence of anticancer activity. New data from a global phase II randomized trial comparing a combination of ARQ 197 plus erlotinib with erlotinib/placebo, in endothelial growth factor receptor inhibitor-naïve patients with locally advanced/metastatic non–small cell lung cancer, demonstrate improvement in progression-free and overall survival with combined therapy. Results were especially pronounced for patients with non–squamous lung cancer histologies, and in particular molecularly defined subgroups including KRAS mutations. These and other data from ARQ 197 clinical trials in hepatocellular, germ-cell, pancreatic (in combination with gemcitabine), and colorectal (in combination with cetuximab and irinotecan) cancers further highlight the potential role of ARQ 197 in existing and emerging anticancer therapeutic regimens.
A Pilot Phase II Study of Valproic Acid for Treatment of Low-Grade Neuroendocrine Carcinoma
Authors: Mohammed Tabraiz A. , Holen Kyle D. , Jaskula-Sztul Renata , Mulkerin Daniel , Lubner Sam J. , Schelman William R. , Eickhoff Jens , Chen Herbert , LoConte Noelle K. 
Published: June 2011

Abstract

Introduction.
Notch1 has been shown to be a tumor suppressor in neuroendocrine tumors (NETs). Previous in vitro studies in NET cell lines have also suggested that valproic acid (VPA), a histone deacetylase inhibitor, can induce Notch1 and that Notch1 activation correlates with a decrease in tumor markers for NETs. Thus, this study aimed to evaluate the role of VPA in treating NETs and to determine whether VPA induced the Notch signaling pathway signaling in vivo.

Patients and Methods.
Eight patients with low-grade NETs (carcinoid and pancreatic) were treated with 500 mg of oral VPA twice a day with dosing adjusted to maintain a goal VPA level between 50 and 100 μg/mL. All patients were followed for 12 months or until disease progression.

Results.
Notch1 signaling was absent in all tumors prior to treatment and was upregulated with VPA. One patient had an unconfirmed partial response and was noted to have a 40-fold increase in Notch1 mRNA levels. Four patients had stable disease as best response. Tumor markers improved in 5 out of 7 patients. Overall, treatment with VPA was well tolerated.

Conclusion.
VPA activates Notch1 signaling in vivo and may have a role in treating low-grade NETs.
Outcomes After Combined Modality Therapy forEGFR-Mutant and Wild-Type Locally Advanced NSCLC
Authors: Mak Raymond H. , Doran Elizabeth , Muzikansky Alona , Kang Josephine , Neal Joel W. , Choi Noah C. , Willers Henning , Jackman David M. , Sequist Lecia V. 
Published: June 2011

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Describe locoregional recurrence rates in EGFR-mutant and wild-type EGFR patients in this study who had locally advanced non-small cell lung cancer that was treated with combined modality therapy, including thoracic radiation therapy.Compare the locoregional recurrence rate in EGFR-mutant and wild-type EGFR patients in this study who had locally advanced non-small cell lung cancer and who were treated without surgery.This article is available for continuing medical education credit at CME.TheOncologist.comBackground.Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well described.Methods.We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan–Meier analysis, the log-rank test, and multivariate Cox regression models.Results.All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations and 94% had stage III disease. Overall, 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, the overall survival (OS) rate was significantly higher in patients with EGFR-mutant tumors than in those with wild-type EGFR tumors (2-year estimate: 92.6% versus 69.0%; p = .04). The 2-year relapse-free survival and distant recurrence rates did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant than in wild-type EGFR patients (17.8% versus 41.7%; p = .005). EGFR-mutant genotype was associated with a lower risk for LRR on multivariate analysis, but not OS, after adjusting for surgery and other potential confounders.Conclusion.We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than wild-type EGFR patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and OS after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies.
Correlates of Quality of Life in Older Adults With Diabetes
Authors: Laiteerapong Neda , Karter Andrew J. , Liu Jennifer Y. , Moffet Howard H. , Sudore Rebecca , Schillinger Dean , John Priya M. , Huang Elbert S. 
Published: June 2011

OBJECTIVE
To evaluate associations between health-related quality of life (HRQL) and geriatric syndromes, diabetes complications, and hypoglycemia in older adults with diabetes.

RESEARCH DESIGN AND METHODS
A race-stratified random sample of 6,317 adults with type 2 or type 1 diabetes, aged 60 to 75 years, enrolled in Kaiser Permanente Northern California, who completed a survey that included a HRQL instrument based on the Short Form 8-item health survey. Administrative records were used to ascertain diagnoses of geriatric syndromes, diabetes complications, and hypoglycemia. Associations were estimated between HRQL and exposures in exposure-specific and combined exposure models (any syndrome, any complication, or hypoglycemia). Conservatively, differences of ≥3 points were considered the minimally important difference in HRQL scores.

RESULTS
HRQL was lower with nearly all exposures of interest. The lowest physical HRQL was associated with amputation. In combined exposure models, geriatric syndromes (−5.3 [95% CI −5.8 to −4.8], P &lt; 0.001) and diabetes complications (−3.5 [−4.0 to −2.9], P &lt; 0.001) were associated with lower physical HRQL. The lowest mental HRQL was associated with depression, underweight (BMI &lt;18 kg/m2), amputation, and hypoglycemia. In combined exposure models, only hypoglycemia was associated with lower mental HRQL (−4.0 [−7.0 to −1.1], P = 0.008).

CONCLUSIONS
Geriatric syndromes and hypoglycemia are associated with lower HRQL to a comparable degree as diabetes complications. Addressing geriatric syndromes and avoiding hypoglycemia should be given as high a priority as preventing diabetes complications in older adults with diabetes.
Skin Intrinsic Fluorescence Is Associated With Hemoglobin A1c and Hemoglobin Glycation Index but Not Mean Blood Glucose in Children With Type 1 Diabetes
Authors: Felipe Dania L. , Hempe James M. , Liu Shuqian , Matter Nate , Maynard John , Linares Carmen , Chalew Stuart A. 
Published: June 2011

OBJECTIVE
To evaluate the relationship between skin advanced glycation end products (sAGEs) with mean blood glucose (MBG), hemoglobin A1c (HbA1c), and MBG-independent, between-patient differences in HbA1c among children with type 1 diabetes.

RESEARCH DESIGN AND METHODS
Children aged 5 to 20 years with type 1 diabetes of at least 1 year duration participated. At a clinic visit, sAGE was estimated noninvasively by measurement of skin intrinsic fluorescence (SIF). SIF data were adjusted to correct for variation in skin pigmentation. MBG-independent, between-patient differences in HbA1c were examined by statistically controlling HbA1c for MBG or alternatively by use of a hemoglobin glycation index (HGI). Results were similar whether HbA1c, MBG, and HGI were analyzed as single values from the time of the SIF examination visit or as the mean values from all available visits of the patient.

RESULTS
HbA1c was correlated with MBG (r = 0.5; P &lt; 0.001; n = 110). HbA1c and HGI, but not MBG, were statistically associated with SIF after adjustment for age, duration of diabetes, race, sex, and BMI z-score. SIF increased with age and duration of diabetes and was higher in girls than boys.

CONCLUSIONS
sAGE levels estimated by SIF increase with age, duration of diabetes, and female sex. sAGE is correlated with MBG-independent biological variation in HbA1c, but not with MBG itself. These results suggest that factors besides MBG that influence HbA1c levels also contribute to accumulation of sAGE.
Erratum to: “Aqueous Phenol and Ethylene Glycol Solutions in Electrohydrodynamic Liquid Bridging”
Authors: Eisenhut Mathias , Guo Xinghua , Paulitsch-Fuchs Astrid , Fuchs Elmar 
Published: June 2011

Abstract
The original version of the article was published in Cent. Eur. J. Chem. 9(3) (2011), pp 391–403. Unfortunately, the original version of this article contains mistakes in the caption of the y-axis of Figs. 5,6 and 10 due to a font conversion problem. The actual units on the y-axis of these figures should be µS cm−1, not mS cm−1.
Synthesis and antimicrobial screening of pyrano[3,2-c]chromene derivatives of 1H-pyrazoles
Authors: Sangani Chetan , Mungra Divyesh , Patel Manish , Patel Ranjan 
Published: June 2011

Abstract
A new series of twenty four derivatives of pyrano[3,2-c]chromene IVa-x bearing 1H-pyrazole were synthesized by a one pot, base-catalyzed cyclocondensation reaction of 1H-pyrazole-4-carbaldehyde Ia-l, malononitrile II and 4-hydroxycoumarin IIIa-b. All the synthesized compounds were characterized by elemental analysis, FT-IR, 1H NMR and 13C NMR spectral data. All the synthesized compounds were screened against six bacterial pathogens, namely B. subtilis, C. tetani, S. pneumoniae, S. typhi, V. cholerae, E. coli and for antifungal activity against two fungal pathogens, A. fumigatus and C. albicans using the broth microdilution MIC method. Some of the compounds were found to be equipotent or more potent than commercial drugs against most of employed strains, as evident from the screening data.
Determination of nickel by chemical vapor generation in situ trapping flame AAS
Authors: Matusiewicz Henryk , Krawczyk Magdalena 
Published: June 2011

Abstract
The analytical performances of coupled chemical vapor generation, integrated atom trap (CVG-IAT) atomizer flame atomic absorption spectrometry (FAAS) system were evaluated for determination of nickel in environmental samples. Nickel chemical vapors are atomized in an air-acetylene flame-heated IAT. A new design of CVG-IAT-FAAS hyphenated technique that would exceed the operational capabilities of existing arrangements (a water-cooled single silica tube, double-slotted quartz tube) permitting construction of an “integrated trap” was investigated. An improvement in limit of detection was achieved compared with that obtained using any of the above atom trapping techniques separately. The concentration limit of detection was 1 ng mL−1 for Ni. The overall efficiencies of the vapor generation process was estimated to be ca. 50%. For a 2 min in situ pre-concentration time, sensitivity enhancement, compared to FAAS, was 200 folds for Ni, using vapor generation atom trapping technique. The sensitivity can be further improved by increasing the collection time. The precision of the measurements for 25 ng mL−1 of Ni was 9% RSD. The accuracy of this method was tested by analyses of NIST SRM 2704 (Buffalo River Sediment), NIST SRM 1648 (Urban Particulate Matter), NIST SRM 2710 (Montana Soil), NBS SRM 1633a (Coal Fly Ash) and NIST SRM 1643e (Trace Element in Water) certified reference materials. The measured Ni content in five reference materials was in satisfactory agreement with the certified values (in the range of 14.3–98 μg g−1). The hyphenated technique was applied for nickel determination in coal fly ash, soil, sediment, sewage and river water.