bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-related Reference Values for Serum Selenium Concentrations in Infants and Children
Authors: Muntau Ania C , Streiter Monika , Kappler Matthias , Röschinger Wulf , Schmid Irene , Rehnert Albert , Schramel Peter , Roscher Adelbert A
Published: January 2020

Background: Children are at particular risk for selenium deficiency, which has potentially serious medical implications. Reliable age-specific reference values for serum selenium concentrations in children are sparse, but are essential for the identification of selenium deficiency and decisions regarding selenium supplementation.

Methods: Using electrothermal atomic absorption spectrometry, we analyzed serum selenium concentrations from 1010 apparently healthy children (age range, 1 day to 18 years) and from 60 patients on a protein-restricted diet because of inborn errors of metabolism. Reference intervals were defined according to recommended guidelines.

Results: Medians for serum selenium concentrations showed a statistically significant age dependency: a decrease from the age <1 month (0.64 μmol/L) to 4 months (0.44 μmol/L); an increase to 0.62 μmol/L in the 4–12 months age group; constant values in children between 1 and 5 years of age (0.90 μmol/L); and an additional slight increase to reach a plateau between 5 and 18 years (0.99 μmol/L). Of 43 children older than 1 year and on a protein-restricted diet, 87% showed serum selenium concentrations below the 2.5 percentile.

Conclusions: Because of nutritional changes, serum selenium concentrations are significantly higher in older children than in infants under 1 year of age. The application of age-adjusted reference values may provide more specific criteria for selenium supplementation. Long-term protein restriction in children is reflected by a failure to achieve higher serum selenium concentrations with increasing age.
Highly Sensitive Cholesterol Assay with Enzymatic Cycling Applied to Measurement of Remnant Lipoprotein-Cholesterol in Serum
Authors: Kishi Koji , Ochiai Koji , Ohta Yohsuke , Uemura Yahiro , Kanatani Kazushi , Nakajima Katsuyuki , Nakamura Masakazu
Published: January 2020

Background: Remnant lipoprotein-cholesterol (RLP-C) concentrations in sera of healthy individuals are very low (0.080–0.437 mmol/L), making conventional cholesterol methods poorly suited to this purpose. We have developed a highly sensitive cholesterol assay (CD method) and applied it to the RLP-C assay.

Methods: The CD shuttled cholesterol reversibly between reduced and oxidized forms in the presence of thio-NAD and NADH. The production rate of thio-NADH correlated with the cholesterol concentration and was measured by the absorbance at 404/500 nm. This CD method was combined with an immunoaffinity separation procedure with specific monoclonal antibodies to apolipoprotein (apo) A1 and apo B-100 and used for RLP-C assay. Results were compared with a RLP-C method that uses cholesterol oxidase, peroxidase, and chromogenic substrate.

Results: The CD method could detect 0.10 × 10−3 mmol/L cholesterol and was at least 5 times more sensitive than the conventional enzymatic method. Within- and between-day imprecision (as CVs) of the RLP-C assay with the CD method was <4%. Regression analysis of RLP-C assays with the new (y) and conventional (x) cholesterol methods yielded: y = 1.02x − 0.008 mmol/L (Sy|x = 0.0065 mmol/L; r = 0.997; n = 297).

Conclusions: Serum RLP-C can be measured by the CD method. The CD method may be useful for other assays that require sensitive cholesterol measurements in biological materials.
Effect of Atorvastatin and Fish Oil on Plasma High-Sensitivity C-Reactive Protein Concentrations in Individuals with Visceral Obesity
Authors: Chan Dick C , Watts Gerald F , Barrett P Hugh R , Beilin Lawrence J , Mori Trevor A
Published: January 2020

Background: Chronic low-grade inflammation may contribute to the increased risk of atherosclerosis in visceral obesity. Statin and fish oil have been reported to have antiinflammatory effects. We studied whether dyslipidemic, obese individuals have increased plasma high-sensitivity C-reactive protein (hs-CRP) concentrations and whether treatment with atorvastatin and fish oil lowered plasma hs-CRP concentrations.

Methods: We compared plasma hs-CRP, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations in 48 obese individuals with the concentrations in 10 lean normolipidemic men. The obese individuals were then randomized to treatment with atorvastatin (40 mg/day), fish oil (4 g/day), atorvastatin plus fish oil, or matching placebo for 6 weeks.

Results: Compared with controls, obese individuals had increased hs-CRP [geometric mean, 2.19 mg/L (95% confidence interval, 2.15–3.15 mg/L) vs 0.49 mg/L (0.30– 0.93 mg/L); P <0.001] and IL-6 [351 pg/L (318–449 pg/L) vs 251 pg/L (211–305 pg/L); P <0.01]. Atorvastatin treatment had a significant main effect of decreasing plasma hs-CRP (−0.87 mg/L; 95% confidence interval, −0.10 to −1.60 mg/L; P <0.01) and IL-6 (−70 pg/L; 10 to −140 pg/L; P <0.01), but this was not seen with fish oil. The reductions in hs-CRP with atorvastatin were not significantly correlated to changes in plasma lipids, IL-6, insulin resistance, or cholesterogenesis. Plasma TNF-α concentrations in obese individuals, however, were neither statistically different from concentrations in the lean controls nor altered with atorvastatin or fish oil treatment.

Conclusions: This study shows that visceral obesity is associated with increased plasma hs-CRP and IL-6 and, hence, a low-grade chronic inflammatory state and that treatment with atorvastatin or atorvastatin with fish oil, but not fish oil alone, reverses this abnormality.
Quantification and Utility of Monosialylated α-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma with Nondiagnostic Serum Total α-Fetoprotein
Authors: Poon Terence CW , Mok Tony SK , Chan Anthony TC , Chan Charles ML , Leong Veronica , Tsui Steven HT , Leung Thomas WT , Wong Herman TM , Ho Stephen KW , Johnson Philip J
Published: January 2020

Background: At concentrations <500 μg/L, serum α-fetoprotein (AFP) has low specificity in the diagnosis of hepatocellular carcinoma (HCC), but monosialylated AFP (msAFP) is more specific for HCC. We describe two strategies for quantitative analysis of msAFP and explore their diagnostic accuracy in cases of HCC with nondiagnostic serum total AFP concentrations.

Methods: We first used isoelectric focusing, Western blot, and densitometry (IEF-Western blot assay). We then developed a second assay, a novel glycosylation immunosorbent assay (GISA), based on the specificity of sialyltransferase and immunosorbent technology. Both assays were used to measure msAFP and msAFP percentage relative to total AFP in sera with nondiagnostic AFP concentrations from 36 patients with newly diagnosed HCC and from 18 patients with liver cirrhosis.

Results: The msAFP percentages and concentrations were significantly higher in the HCC patient group regardless of the quantification methods. The msAFP concentrations and msAFP percentages obtained by the two assays were highly correlated (r = 0.70 and 0.49, respectively). For discrimination of HCC with nondiagnostic serum total AFP from liver cirrhosis, the areas under the ROC curves were 0.81 (95% confidence interval, 0.70–0.92) for msAFP by IEF-Western blot assay, 0.73 (0.58–0.87) for msAFP by GISA, 0.89 (0.80–0.97) for msAFP percentage by IEF-Western blot assay, and 0.74 (0.59–0.89) for msAFP percentage by GISA.

Conclusions: Both the serum concentration and percentage of msAFP are potential diagnostic markers for HCC with nondiagnostic AFP. GISA can quantify a specific glycoform of a serologic marker.
Relationship between Genetic Polymorphisms of Alcohol-metabolizing Enzymes and Changes in Risk Factors for Coronary Heart Disease Associated with Alcohol Consumption
Authors: Hashimoto Yoshiaki , Nakayama Toshifumi , Futamura Azusa , Omura Miho , Nakarai Hideo , Nakahara Kazuhiko
Published: January 2020

Background: There are large individual variations in the responses of risk factors for coronary heart disease to alcohol consumption. To clarify the factors responsible for these individual variations, we studied the relationship between blood pressure, serum lipids, and uric acid and the genetic polymorphisms of alcohol dehydrogenase (ADH) 2 and aldehyde dehydrogenase (ALDH) 2 in alcohol drinkers.

Methods: We examined 133 male workers who drank >300 g of alcohol per week. Information regarding lifestyle habits was obtained by questionnaire. The ADH2 genotype was determined by PCR and subsequent digestion with MaeIII. The ALDH2 genotype was determined based on amplified product length polymorphisms.

Results: When the workers were divided into three groups: the ADH21/21, ADH21/22, and ADH22/22 groups, the mean triglycerides and γ-glutamyl transpeptidase concentrations were significantly higher in the ADH22/22 group than in the ADH21/21 group. In addition, multiple logistic regression analysis showed that the frequencies of individuals whose systolic blood pressure, triglycerides, and uric acid values were in the highest one third were significantly higher in the ADH22/22 group than in the ADH21/21 group. In contrast, no difference was observed between the ALDH21/21 and (ALDH21/22 + ALDH22/22) groups with regard to the mean value of any variable and to the frequency of individuals with any variable value in the highest one third.

Conclusion: Individuals with the ADH21/21 genotype might suffer fewer negative effects of drinking.
Plasma Nucleic Acids in the Diagnosis and Management of Malignant Disease
Authors: Johnson Philip J , Lo YM Dennis
Published: January 2020

Background: There is a need for development of molecular markers of cancer that can be used clinically for the detection, prognostication, and monitoring of cancer. Recently, there has been much interest in the potential use of nucleic acid markers in plasma and serum for this purpose.

Approach: We reviewed published literature up to 2002 on the topic, with a particular emphasis on reports published between 1996 and 2002.

Content: The nucleic acid markers described in plasma and serum include oncogene mutations/amplifications, microsatellite alterations, and gene rearrangements. Such markers have been described in many cancer types, including lung, colon, and breast. Epigenetic alterations, such as aberrant promoter methylation, have been identified in plasma and serum. Viral nucleic acid markers, such as Epstein–Barr virus DNA in plasma and serum, are reviewed in detail with regard to their application to virus-associated cancers such as nasopharyngeal carcinoma and various lymphomas. More recently, mitochondrial DNA and tumor-related mRNAs have been identified in plasma and serum from patients with several types of tumors.

Conclusions: Circulating nucleic acids are an emerging class of molecular tumor markers. Their wide applicability and clinical relationship with the malignant state will likely grant them increasing clinical importance in the near future.
Measurement of Prostate-specific Antigen by Use of a Novel Blood Collection and Analytical System
Authors: Grzeda Barbara R , Le Bui Tuan , Warner Cheryl N , Pirucki Tracy L , Dewey Lisa M , Babich Milan , Maggiore Jack A
Published: January 2020

Background: Prostate-specific antigen (PSA) is widely used in the detection and monitoring of prostate cancer. We developed a system for the self-collection and transport of capillary whole blood for PSA analysis, with the goal of reducing phlebotomy visits and, thus, increasing the access and utilization of PSA in prostate cancer screening and monitoring.

Methods: The blood collection device [BIOSAFE Blood Transport System (BTSTM)] collects 70 μL of blood through a heparin-coated material into 200 μL of stabilizing solution. The diluted whole blood is used for measurement of PSA by a modified version of the Hybritech® Tandem-MP PSA Assay. Results were compared for matched samples of professionally and self-collected BTS blood and for matched BTS samples sera from blood collected by venipuncture. Imprecision for the whole-blood PSA measurement was estimated from analysis of whole-blood controls in duplicate, twice per day, over 20 days.

Results: BTS samples (n = 140) collected by a qualified healthcare professional compared with serum samples yielded the regression equation: y =1.02x + 0.04 (Sy|x = 0.35; r = 0.99). Comparison of the results for samples (n = 128) collected by the patient without professional assistance with serum samples yielded: y = 1.08x + 0.02 (Sy|x = 0.31; r = 0.99). The between-run CVs at 0.069, 0.53, 2.9, and 10.7 μg/L were 21%, 6.0%, 3.5%, and 3.8%, respectively. PSA was stable in BTS samples stored for 21 days at 18–24 °C and for 7 days at 37 °C.

Conclusion: The BIOSAFE BTS system allows accurate and convenient measurement of circulating PSA by a precise method for diluted whole blood.
Quantitative Real-Time Reverse Transcription-PCR Assay for Urokinase Plasminogen Activator, Plasminogen Activator Inhibitor Type 1, and Tissue Metalloproteinase Inhibitor Type 1 Gene Expressions in Primary Breast Cancer
Authors: Castelló Remedios , Estellés Amparo , Vázquez Carlos , Falcó Cristina , España Francisco , Almenar Sergio M , Fuster Carlos , Aznar Justo
Published: January 2020

Background: The plasminogen activation system and matrix metalloproteinases (MMPs) play a key role in the degradation of basement membrane and extracellular matrix in tissue remodeling, cancer cell invasion, and metastasis.

Methods: Quantitative real-time reverse-transcription-PCR (RT-PCR) assays were developed to quantify urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1), and tissue metalloproteinase inhibitor type 1 (TIMP-1) mRNA in 54 breast cancer tissues. Gene fragments were amplified in a LightCycler real-time PCR system using gene-specific primers and SYBR Green I. The results were normalized to β-actin mRNA. We also quantified antigen and functional concentrations of these components.

Results: The intra- and interassay variabilities for mRNA quantification showed mean SDs for the crossing point of 0.12 and 0.15 cycles, respectively. PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations and PAI-1 and uPA functional concentrations increased with tumor severity; the increase was statistically significant for PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations and for uPA functional concentrations. Node-positive patients showed significantly higher PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations than those who were node negative.

Conclusions: Quantitative real-time RT-PCR is a highly sensitive, reproducible, and fast method for measuring gene expression of PAI-1, uPA, and TIMP-1 in breast cancer. These components may be involved in breast cancer development, and increased mRNA expression may be associated with a worse prognosis.
Development and Evaluation of a Practical ELISA for Human Urinary Lipocalin-Type Prostaglandin D Synthase
Authors: Oda Hiroshi , Shiina Yasuhiko , Seiki Kousuke , Sato Nobuyuki , Eguchi Naomi , Urade Yoshihiro
Published: January 2020

Background: Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS) is significantly increased in patients with chronic renal failure, but its diagnostic potential in less advanced stages of renal diseases remains to be elucidated.

Methods: Six mouse monoclonal antibodies (MAbs) were raised against recombinant human L-PGDS. We constructed a sandwich ELISA with two MAbs that recognized different epitopes with high affinities and assessed its assay performance and clinical utility with urine samples from healthy controls, diabetic patients, and patients with various renal diseases.

Results: Western blot analyses with NH2-terminus-truncated L-PGDS mapped the epitopes to Ala23–Val28 (MAb-7F5 and -10A3), Ser52–Ala73 (MAb-9A6), Tyr107–Val120 (MAb-1B7 and -6F5), and Gly140–Pro155 (MAb-6B9). A sandwich ELISA was constructed with MAb-1B7 and -7F5, the Kd values of which were 3.6 and 3.9 nmol/L, respectively, for native L-PGDS. Recoveries were 91–111%, and intra- and interassay CVs were <6% and <9%, respectively. The ELISA showed parallelism of standard and urine samples and no significant interference by a variety of urinary constituents. Urinary L-PGDS excretion was significantly increased in patients with diabetic nephropathy, IgA nephropathy, and chronic glomerulonephritis even when serum creatinine was not increased. In patients with renal diseases, urinary L-PGDS was correlated with urinary albumin (r = 0.64; P <0.0001), N-acetyl-β-d-glucosaminidase (r = 0.43; P <0.001), and serum creatinine (r = 0.66; P <0.0001). At a cutoff value of 284 mg/mol creatinine, the assay had sensitivities of 74% for diabetic nephropathy and 83% for chronic glomerulonephritis and a specificity of 93%.

Conclusions: This ELISA system is suitable for measurement of urinary L-PGDS in a routine clinical assay and may be useful to detect less advanced stages of renal diseases.
Simultaneous Analysis of Nicotine, Nicotine Metabolites, and Tobacco Alkaloids in Serum or Urine by Tandem Mass Spectrometry, with Clinically Relevant Metabolic Profiles
Authors: Moyer Thomas P , Charlson Joel R , Enger Robert J , Dale Lowell C , Ebbert Jon O , Schroeder Darrell R , Hurt Richard D
Published: January 2020

Background: Assessment of nicotine metabolism and disposition has become an integral part of nicotine dependency treatment programs. Serum nicotine concentrations or urine cotinine concentrations can be used to guide nicotine patch dose to achieve biological concentrations adequate to provide the patient with immediate relief from nicotine withdrawal symptoms, an important factor in nicotine withdrawal success. Absence of nicotine metabolites and anabasine can be used to document abstinence from tobacco products, an indicator of treatment success.

Methods: The procedure was designed to quantify nicotine, cotinine, trans-3′-hydroxycotinine, anabasine, and nornicotine in human serum or urine. The technique required simple extraction of the sample with quantification by HPLC–tandem mass spectrometry.

Results: The procedure for simultaneous analysis of nicotine, its metabolites, and tobacco alkaloids simultaneously quantified five different analytes. Test limit of quantification, linearity, imprecision, and accuracy were adequate for clinical evaluation of patients undergoing treatment for tobacco dependency. The test readily distinguished individuals who had no exposure to tobacco products from individuals who were either passively exposed or were abstinent past-tobacco users from those who were actively using a tobacco or nicotine product.

Conclusions: Nicotine, cotinine, trans-3′-hydroxycotinine, nornicotine, and anabasine can be simultaneously and accurately quantified in either serum or urine by HPLC–tandem mass spectrometry with imprecision <10% at physiologic concentrations and limits of quantification ranging from 0.5 to 5 μg/L. Knowledge of serum or urine concentrations of these analytes can be used to guide nicotine replacement therapy or to assess tobacco abstinence in nicotine dependency treatment. These measurements are now an integral part of the clinical treatment and management of patients who wish to overcome tobacco dependence.
Interlaboratory Variation of Plasma Total Homocysteine Measurements: Results of Three Successive Homocysteine Proficiency Testing Surveys
Authors: Hanson Naomi Q , Eckfeldt John H , Schwichtenberg Kerry , Aras Ömer , Tsai Michael Y
Published: January 2020

Background: Numerous studies have demonstrated that increased plasma total homocysteine (tHcy), whether measured after fasting or after a methionine load, is associated with increased risk for cardiovascular and thromboembolic diseases. However, little information is available regarding interlaboratory variation of tHcy measurements, especially at the increased tHcy concentrations observed after loading.

Methods: We conducted three Homocysteine Proficiency Testing Surveys at 6-month intervals. Sets of five plasma pools with endogenous tHcy concentrations ranging from 5 to 48 μmol/L were sent to participants. We received 11, 23, and 17 responses in the first, second, and third surveys, respectively. The following methods were used by participating laboratories: fluorescence polarization immunoassay (FPIA); HPLC with fluorescent detection (HPLC-FD), further subdivided by type of reduction/derivatization; HPLC with electrochemical detection (HPLC-ED); amino acid analyzer with ninhydrin detection; and liquid chromatography–electrospray tandem mass spectrometry (LC-MS/MS).

Results: In surveys 1 and 2, no notable differences among the mean tHcy values obtained by the different methods performed were observed. In survey 3, tHcy values obtained by the FPIA method were significantly lower (P <0.05) at increased tHcy concentrations (34 μmol/L) compared with values obtained by HPLC-FD regardless of reduction/derivatization agents used. Our laboratory confirmed the observation that tHcy values obtained by the FPIA method differed from those obtained by HPLC-FD at increased tHcy concentrations by reanalyzing each pool 10 times by FPIA and HPLC-FD using tributylphosphine–ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (P <0.001 for tHcy >19 μmol/L). The mean among-method variations in surveys 1, 2, and 3 were 19%, 12%, and 9.6%, respectively. When results of the three surveys were combined, the mean among-method variation on 170 samples was 13%. Within-method variation was lowest for the FPIA method (4.4%), and ranged from 11–20% for HPLC methods.

Conclusions: Various degrees of imprecision and lack of correlation among tHcy methods indicate that there is a need to improve analytical precision, decrease analytical difference, and standardize tHcy measurements among laboratories.
Comparison of Anti-Transglutaminase ELISAs and an Anti-Endomysial Antibody Assay in the Diagnosis of Celiac Disease: A Prospective Study
Authors: Carroccio Antonio , Vitale Giustina , Di Prima Lidia , Chifari Nadia , Napoli Salvatore , La Russa Cristina , Gulotta Gaspare , Averna Maurizio R , Montalto Giuseppe , Mansueto Serafino , Notarbartolo Alberto
Published: January 2020

Background: Most studies of anti-transglutaminase (anti-tTG) assays have considered preselected groups of patients. This study compared the sensitivity, specificity, and predictive value of an immunofluorescence method for anti-endomysial antibodies (EmAs) and two anti-tTG ELISAs, one using guinea pig tTG (gp-tTG) and the other human tTG (h-tTG) as antigen, in consecutive patients investigated for suspected celiac disease (CD).

Methods: We studied 207 consecutive patients (99 men, 108 women; age range, 17–84 years) who underwent intestinal biopsy for suspected CD. Patients presented with one or more of the following: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits, constipation, pain in the joints, and dermatitis. At entry to the study, an intestinal biopsy was performed and a serum sample was taken for IgA EmAs, anti-gp-tTG, and anti-h-tTG.

Results: Intestinal histology showed that 24 patients had partial or total villous atrophy; in these patients the diagnosis of CD was confirmed by follow-up. The remaining 183 patients had villous/crypt ratios that were within our laboratory’s reference values and were considered controls. Serum EmAs, anti-gp-tTG, and anti-h-tTG were positive in all 24 CD patients; in the control group, none were positive for serum EmAs, but 15 of 183 (8.2%) were positive for anti-gp-tTG, and 6 of 183 (3.3%) were positive for anti-h-tTG. Sensitivity was 100% for all assays, whereas specificity was 100% for the EmA, 92% for the anti-gp-tTG, and 97% for the anti-h-tTG assay. The negative predictive value was 100% for all assays; the positive predictive value was 100% for the EmA, 80% [95% confidence interval (CI), 65–95%] for the anti-h-tTG (P = 0.03 vs EmA) and 60% (95% CI, 44–76%) for the anti-gp-tTG assay (P = 0.0002 vs EmA). Areas (95% CIs) under the ROC curves were 0.987 (0.97–1.0) for anti-h-tTG and 0.965 (0.94–0.99) for anti-gp-tTG. Most of the patients testing false positive for anti-tTG had Crohn disease or chronic liver disease.

Conclusions: Although both anti-tTG ELISAs showed optimum sensitivity, their lack of specificity yielded positive predictive values significantly lower than those for the EmA assay.
Quantitative Analysis of p40/p46 and p69/p71 Forms of 2′,5′-Oligoadenylate Synthetase mRNA by Competitive PCR and Its Clinical Application
Authors: Takahashi Akira , Iwasaki Yoshiaki , Miyaike Jiro , Taniguchi Hideaki , Shimomura Hiroyuki , Hanafusa Tadashi , Yumoto Yasuhiro , Moriya Akio , Koide Norio , Tsuji Takao
Published: January 2020

Background: 2′,5′-Oligoadenylate synthetases (2-5AS) are type I interferon (IFN)-induced proteins with antiviral capacity. Three major forms of 2-5AS with distinct enzymatic activities have been described in IFN-treated human cells. We measured distinct forms of 2-5AS mRNA to analyze the relationship with its enzymatic activity and response to IFN therapy in chronic hepatitis C.

Methods: We established a method to quantify p40/p46 and p69/p71 forms of 2-5AS mRNA by use of reverse transcription followed by competitive PCR. The 2-5AS mRNA concentrations were measured in peripheral blood mononuclear cells from 40 patients with chronic hepatitis C and 28 control individuals.

Results: Reconstitution experiments and comparison with Northern blot analyses revealed that our method accurately and linearly quantified 2-5AS mRNA. 2-5AS mRNA concentrations and 2-5AS enzymatic activity were correlated (P <0.03). Our data demonstrated a correlation in 2-5AS mRNA between p40/p46 and p69/p71 (P <0.02), indicating a similar regulation of the expression of these genes. Our data also demonstrated that pretreatment concentrations of 2-5AS mRNA correlated with responses to IFN therapy in chronic hepatitis C.

Conclusions: Our method for measuring 2-5AS mRNA concentrations could provide an important marker for selecting patients for IFN therapy and may be useful for the development of more effective therapeutic strategies for chronic hepatitis C.
Modification of Fully Automated Total Iron-binding Capacity (TIBC) Assay in Serum and Comparison with Dimension TIBC Method
Authors: Yamanishi Hachiro , Iyama Shigeru , Yamaguchi Yoshihisa , Kanakura Yuzuru , Iwatani Yoshinori
Published: January 2020

Background: We previously reported the development of a fully automated assay for total iron-binding capacity (TIBC) in serum, using a multipurpose automated analyzer. However, this method requires four different reagents and is thus useful only with a limited number of available analyzers. We simplified our original assay and compared the analytical performance of the modified method with that of a commercial, fully automated TIBC assay (Dimension® TIBC assay).

Methods: We simplified our original method to require only three reagents. Calibration was also altered and was performed with human transferrin standard solutions. An advantage of this method is that it does not require separation of excess unbound iron after the first step of transferrin saturation. Unbound iron is eliminated by formation of a complex with the chromogenic reagent ferrozine in the second step. Iron dissociated from transferrin by acidic pH reacts with ferrozine to form a colored complex in the final step, and the increase in absorbance at 570/660 nm is directly proportional to the TIBC measured. TIBC values were determined for 49 healthy individuals and 148 patients with this modified TIBC assay and with a commercial, fully automated TIBC method (Dimension clinical chemistry system), and calculation of TIBC based on the sum of the serum iron and unsaturated iron-binding capacity was performed for 97 patients.

Results: The within-run CVs for the modified TIBC assay and the Dimension TIBC assay were <4.8% and <2.4%, and the between-run CVs were 1.2% and 1.7%, respectively. The dilution curves were linear for TIBC values up to at least 180 μmol/L with both methods. TIBC values obtained by our method were linearly correlated with serum transferrin concentrations (r = 0.984; Sy|x = 3.18 μmol/L; P <0.001). The correlation between the values obtained with the present method (y) and those obtained with the Dimension TIBC method (x) was y = 1.04x + 1.19 μmol/L (r = 0.985; Sy|x = 2.47 μmol/L), and with the calculation method (x) was y = 1.18x + 2.62 μmol/L (r = 0.976; Sy|x = 3.27 μmol/L).

Conclusions: Our modified, fully automated TIBC assay performed similarly to the Dimension TIBC assay and is adaptable for use with many multipurpose automated analyzers.
Skill-Biased Management: Evidence from Manufacturing Firms
Authors: Feng Andy , Valero Anna
Published: January 2020

This article investigates the link between management practices and workforce skills in manufacturing firms, exploiting geographical variation in the supply of human capital. Skills measures are constructed using newly compiled data on universities and regional labour markets across 19 countries. Consistent with management practices being complementary with skills, we show that firms further away from universities employ fewer skilled workers and are worse managed, even after controlling for a rich set of observables and fixed effects. Analysis using regional skill premia suggests that variation in the price of skill drives these relationships.
Learner Initiatives in the EFL Classroom: a Public/Private Phenomenon
Authors: Donald Shane
Published: January 2020

This paper examines how a teacher responds to ‘learner initiatives’ during classroom instruction. Learner initiatives refer to students making ‘uninvited’ contributions in class when not selected as the next speaker. This paper focuses on learners initiating an interactional sequence through asking the teacher a question. Using conversation analysis, this research describes two practices adopted by a teacher when responding to such learner initiatives. These practices shape how learners participate within learner-initiated interactional sequences and hence the opportunities that occur for learning the target language. The teacher utilizes recipient design to either better understand learner queries or explicitly answer learner questions as part of dealing with learner initiatives. This paper contributes to understanding of how learner initiatives are managed by teachers and has a role to play in teacher education by raising practitioner awareness of how this aspect of classroom interaction can be managed to further learner participation.
Association between depression and hypertension using classic and revised blood pressure thresholds
Authors: DeMoss Dustin S , Teigen Kari J , Claassen Cynthia A , Fisk Mandy J , Blair Somer E , Bakre Sulaimon A , Hurd Cheryl L , Rush Augustus J
Published: January 2020

Background

In a primary care population, the relationship between treatment of depression and hypertension (HTN) under the recently revised American College of Cardiology and American Heart Association HTN thresholds for diagnosing HTN is unknown.

Objective

To compare the association between changes in severity of co-occurring depression and HTN over time using the newly revised versus previous HTN guidelines.

Methods

In this retrospective cohort study, outpatients ≥18 years (n = 3018) with clinically significant depressive symptoms and elevated blood pressure at baseline were divided into a ‘revised’ guideline group (baseline blood pressure ≥130/80 mmHg), a ‘classic’ guideline group (≥140/90 mmHg) and a ‘revised-minus-classic’ group (≥130/80 and <140/90 mmHg). Depressive symptom change was assessed using the Patient Health Questionnaire-9 (PHQ-9). Correlations between changes in PHQ-9 scores and HTN levels by group over a 6- to 18-month observation period were assessed using robust regression analysis.

Results

There were demographic and clinical differences between groups. A total of 41% of study subjects (1252/3018) had a visit during the follow-up period where additional PHQ-9 and HTN results were available. Depressive symptom change was unrelated to change in blood pressure in the revised and revised-minus-classic groups. The classic HTN group demonstrated a clinically insignificant change in systolic blood pressure for each unit change in PHQ-9 score (β = 0.23, P-value =0.02).

Conclusions

Although a statistically significant association between reduced HTN levels and improvement in depressive symptoms was demonstrated under classic HTN guidelines, there was no clinically meaningful association between treatment of depression and improved HTN levels under either guideline.
Relations of Executive Function and Physical Performance in Middle Adulthood: A Prospective Investigation in African American and White Adults
Authors: Leibel Daniel K , Williams Megan R , Katzel Leslie I , Evans Michele K , Zonderman Alan B , Waldstein Shari R
Published: January 2020

Objectives

Previous studies in older adults found robust associations between executive functions (EF) and physical performance, as well as sociodemographic variation in physical performance decline. To examine these associations earlier in the adult lifespan, we investigated relations of EF, race, and sex with age-related physical performance decline during middle adulthood.

Method

Participants were 2,084 urban-dwelling adults (57.2% female; 57.8% African American; 37.3% living in poverty; mean baseline age = 48.1) from the Healthy Aging in Neighborhoods of Diversity across the Life Span study. Mixed-effects regression was used to examine interactive relations among EF, race, sex, and age (indexing time) with change in dominant and nondominant handgrip strength and lower extremity strength over approximately 5 years. All analyses adjusted for poverty status, and subsequently adjusted for education, body mass index, hypertension, and diabetes.

Results

There were no significant prospective associations between EF and decline in physical performance measures. Significant cross-sectional associations revealed that lower EF was associated with worse performance on all physical performance measures averaged across both time points (p < .05). A significant two-way interaction of Sex × Age (p = .019) revealed that men experienced greater age-related decline in lower extremity strength than women.

Discussion

Findings did not reveal prospective associations between EF and physical performance decline in middle adulthood. However, they identified robust cross-sectional associations between EF and physical performance, and unexpectedly greater decline in lower extremity strength in men than women. Ultimately, these findings may inform prevention and intervention strategies targeting groups at risk for poorer physical function status and decline.
How Can the Arts Influence the Attitudes of Dementia Caregivers? A Mixed-Methods Longitudinal Investigation
Authors: Windle Gill , Caulfield Maria , Woods Bob , Joling Karlijn
Published: January 2020

Background and Objectives

Arts activities can improve social connectedness and foster reciprocity between people living with dementia and their caregivers. The extent to which the arts can help shape attitudes towards dementia remains unclear. This paper explores the impact of a 12-week visual arts program “Dementia and Imagination” on the attitudes of family and professional caregivers through a mixed-methods longitudinal investigation, underpinned by a conceptual framework of the arts in dementia care.

Research Design and Methods

One hundred and forty-six family and professional caregivers were recruited across three settings in England and Wales (residential care homes, a county hospital, and community venues). Quantitative and qualitative data on caregivers’ attitudes and perceptions of the impact of the arts program were collected through interviews at three time points.

Results

Thematic analysis identified four themes shared across the caregivers: (1) Recognizing capabilities, (2) Social connectedness, (3) Improvements to well-being, and (4) Equality and personhood. Two further themes were distinct to family caregivers: (5) Duration of the effects of the art program, and (6) Enriched perspective. The final theme Inspiring professional development was distinct to the professional caregivers. The quantitative analysis found no effect for caregivers’ attitude change over time. Family caregivers scored significantly lower than professional caregivers at each of the three time points.

Discussion and Implications

Art programs have the potential to make visible the capabilities of the people living with dementia, enabling caregivers to see the person behind the condition. This study highlights practice implications for future implementation, such as the role of the arts in dementia care education.
China and Russia in R2P debates at the UN Security Council
Authors: Chen Zheng , Yin Hang
Published: January 2020

While China and Russia's general policies towards the Responsibility to Protect (R2P) are similar, the two reveal nuanced differences in addressing specific emergencies. Both express support for the first two pillars of R2P while resisting coercive intervention under its aegis, as they share anxieties of domestic political security and concerns about their international image. Nonetheless, addressing cases like the Syrian crisis, Russian statements are more assertive and even aggressive while Chinese ones are usually vague and reactive. This article highlights the two states’ different tones through computer-assisted text analyses. It argues that diplomatic styles reflect Russian and Chinese perceptions of their own place in the evolving international order. Experiences in past decades create divergent reference points and status prospects for them, which leads to their different strategies in signalling Great Power status. As Beijing is optimistic about its status-rising prospects, it exercises more self-restraint in order to avoid external containments and is reluctant to act as an independent ‘spoiler’. Meanwhile, Moscow interprets its Great Power status more from a frame of ‘loss’ and therefore is inclined to adopt a sterner approach to signal its status. Although their policies complement each other on many occasions, there is nothing akin to a Sino–Russian ‘bloc’.
Using a cross-cohort comparison design to test the role of maternal smoking in pregnancy in child mental health and learning: evidence from two UK cohorts born four decades apart
Authors: Sellers Ruth , Warne Naomi , Rice Frances , Langley Kate , Maughan Barbara , Pickles Andrew , Thapar Anita , Collishaw Stephan
Published: January 2020

Background

Maternal smoking in pregnancy is associated with low birth weight (LBW), child conduct problems, hyperactivity and lower cognitive attainment, but associations may reflect measured and unmeasured confounding. Cross-cohort designs can aid causal inference through comparison of associations across populations with different confounding structures. We compared associations between maternal smoking in pregnancy and child conduct and hyperactivity problems, cognition and LBW across two cohorts born four decades apart.

Methods

Two national UK cohorts born in 1958 (n = 12 415) and 2000/01 (n = 11 800) were compared. Maternal smoking in pregnancy and child birth weight was assessed at or shortly after birth. Parents rated children’s conduct problems and hyperactivity, and children completed standardized tests of reading and mathematics.

Results

Maternal smoking in pregnancy was less common and more strongly associated with social disadvantage in 2000/01 compared with 1958 (interactions P < 0.001). Maternal smoking in pregnancy was robustly and equivalently associated with infant LBW in both cohorts [interactions: boys odds ratio (OR) = 1.01 (0.89, 1.16), P = 0.838; girls OR = 1.01 (0.91, 1.17), P = 0.633]. Maternal smoking was more strongly associated with conduct problems, hyperactivity and reading in the 2000/01 cohort (interactions P < 0.001).

Conclusions

Marked cross-cohort change in associations between maternal smoking and child conduct problems, hyperactivity and reading highlights the likely role of confounding factors. In contrast, association with LBW was unaffected by change in prevalence of maternal smoking and patterns of confounding. The study highlights the utility of cross-cohort designs in helping triangulate conclusions about the role of putative causal risk factors in observational epidemiology.
Abelian Groups Are Polynomially Stable
Authors: Becker Oren , Mosheiff Jonathan
Published: January 2020

In recent years, there has been a considerable amount of interest in stability of equations and their corresponding groups. Here, we initiate the systematic study of the quantitative aspect of this theory. We develop a novel method, inspired by the Ornstein–Weiss quasi-tiling technique, to prove that abelian groups are polynomially stable with respect to permutations, under the normalized Hamming metrics on the groups $\textrm{Sym}(n)$. In particular, this means that there exists $D\geq 1$ such that for $A,B\in \textrm{Sym}(n)$, if $AB$ is $\delta $-close to $BA$, then $A$ and $B$ are $\epsilon $-close to a commuting pair of permutations, where $\epsilon \leq O\left (\delta ^{1/D}\right )$. We also observe a property-testing reformulation of this result, yielding efficient testers for certain permutation properties.
The Changing Global Epidemiology of Measles, 2013–2018
Authors: Patel Minal K , Antoni Sebastien , Nedelec Yoann , Sodha Samir , Menning Lisa , Ogbuanu Ikechukwu U , Gacic Dobo Marta
Published: January 2020

Background

Measles incidence and mortality rates have significantly decreased since vaccine introduction. Despite this progress, however, there has been a global resurgence of measles. To understand the current global epidemiology, we analyzed measles surveillance data.

Methods

We analyzed data on measles cases from 2013–2018 reported to the World Health Organization. Univariate analysis was undertaken based on age, vaccination history, onset year, World Health Organization region, and World Bank income status for the country where the case was reported, and a surrogate indicator of the historical strength of the country’s immunization program. Annual incidence and a 2013–2018 mean country incidence per million were calculated.

Results

From 2013 through 2018, there were 899 800 reported measles cases, of which 57% occurred unvaccinated or undervaccinated persons, with an unknown vaccination history in another 30%. Lower-middle-income countries accounted for 66% of cases, 23% occurred in persons ≥15 years of age. In countries with stronger historical vaccination programs and higher country income, case patients had higher median ages.

Conclusions

Although most measles case patients are <15 years of age, an age shift is seen in countries with a higher income or a stronger historical vaccination program. Countries must strengthen immunization programs to achieve high vaccination coverage; some must undertake strategies to reach persons ≥15 years of age and close immunity gaps.
What's Feminist about Feminist Foreign Policy? Sweden's and Canada's Foreign Policy Agendas
Authors: Thomson Jennifer
Published: January 2020

Across politics and public discourse, feminism is experiencing a global renaissance. Yet feminist academic work is divided over the burgeoning use of the term, particularly in reference to economic and international development policy. For some, feminism has been co-opted for neoliberal economic ends; for others, it remains a critical force across the globe. This article explores the nascent feminist foreign policies of Sweden and Canada. Employing a discourse analysis of both states’ policy documents, it asks what the term “feminist” meant in preliminary attempts at constructing a feminist foreign policy. It argues that although both use the term “feminist,” they understand the term very differently, with Sweden centering it in domestic and international commitments to change, while Canada places greater emphasis on the private sector. This suggests that this policy agenda is still developing its central concepts, and is thus ripe for intervention on the part of policymakers and civil society organizations.
Illicit Military Behavior as Exceptional and Inevitable: Media Coverage of Military Sexual Violence and the “Bad Apples” Paradox
Authors: MacKenzie Megan , Gunaydin Eda , Chaudhuri Umeya
Published: January 2020

How can we understand consistent public support and trust of the military even in climates of high rates of public awareness about military sexual violence? This article examines how the phenomenon of military sexual violence is mediated to the public through a media content and discourse analysis of newspaper reportage about military sexual violence in Australia. The analysis covers an almost thirty-year period (1989–2016) during which several “sex scandals,” some of international import, broke out. We analyze several frames used to depict the issue and conclude that military sex scandals, like other illicit military behaviors, tend to be publicly framed either as (1) a rarity that is atypical of the institution (“bad apples”) or (2) inevitable and so typical of the institution as to be unremarkable. The article then seeks to demonstrate that these seemingly disparate frames are not contradictory, but rather unify into a singular narrative. The narrative cohering these disparate frames is that military sexual violence is a phenomenon that cannot be prevented or addressed and is therefore unproblematic for the institution.
Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015–16
Authors: Lan Pham Thi , Golparian Daniel , Ringlander Johan , Van Hung Le , Van Thuong Nguyen , Unemo Magnus
Published: January 2020

Objectives

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae, compromising gonorrhoea treatment, is a threat to reproductive health globally. South-East and East Asia have been major sources of emergence and subsequent international spread of AMR gonococcal strains during recent decades. We investigated gonococcal isolates from 2011 and 2015–16 in Vietnam using AMR testing, WGS and detection of AMR determinants.

Methods

Two hundred and twenty-nine gonococcal isolates cultured in 2015–16 (n = 121) and 2011 (n = 108) in Vietnam were examined. AMR testing was performed using Etest and WGS with Illumina MiSeq.

Results

Resistance among the 2015–16 isolates was as follows: ciprofloxacin, 100%; tetracycline, 79%; benzylpenicillin, 50%; cefixime, 15%; ceftriaxone, 1%; spectinomycin, 0%; and 5% were non-WT to azithromycin. Eighteen (15%) isolates were MDR. The MIC range for gentamicin was 2–8 mg/L. Among the 2015–16 isolates, 27% (n = 33) contained a mosaic penA allele, while no isolates had a mosaic penA allele in 2011. Phylogenomic analysis revealed introduction after 2011 of two mosaic penA-containing clones (penA-10.001 and penA-34.001), which were related to cefixime-resistant strains spreading in Japan and Europe, and a minor clade (eight isolates) relatively similar to the XDR strain WHO Q.

Conclusions

From 2011 to 2015–16, resistance in gonococci from Vietnam increased to all currently and previously used antimicrobials except ceftriaxone, spectinomycin and tetracycline. Two mosaic penA-containing clones were introduced after 2011, explaining the increased cefixime resistance. Significantly increased AMR surveillance, antimicrobial stewardship and use of WGS for molecular epidemiology and AMR prediction for gonococcal isolates in Vietnam and other Asian countries are crucial.