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1.
Emerg Infect Dis ; 30(3): 499-509, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38407176

ABSTRACT

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.


Subject(s)
Tuberculosis, Multidrug-Resistant , Tuberculosis , Male , Humans , Vietnam/epidemiology , Tuberculosis, Multidrug-Resistant/epidemiology , Asia , Spatial Analysis
2.
Analyst ; 149(5): 1597-1608, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38291984

ABSTRACT

Antibiotics are compounds that have a particular mode of action upon the microorganism they are targeting. However, discovering and developing new antibiotics is a challenging and timely process. Antibiotic development process can take up to 10-15 years and over $1billion to develop a single new therapeutic product. Rapid screening tools to understand the mode of action of the new antimicrobial agent are considered one of the main bottle necks in the antimicrobial agent development process. Classical approaches require multifarious microbiological methods and they do not capture important biochemical and organism therapeutic-interaction mechanisms. This work aims to provide a rapid antibiotic-antimicrobial biochemical diagnostic tool to reduce the timeframes of therapeutic development, while also generating new biochemical insight into an antimicrobial-therapeutic screening assay in a complex matrix. The work evaluates the effect of antimicrobial action through "traditional" microbiological analysis techniques with a high-throughput rapid analysis method using UV-VIS spectroscopy and chemometrics. Bacteriostatic activity from tetracycline and bactericidal activity from amoxicillin were evaluated on a system using non-resistant Escherichia coli O157:H7 by confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and UV-VIS spectroscopy (high-throughput analysis). The data were analysed using principal component analysis (PCA) and support vector machine (SVM) classification. The rapid diagnostic technique could easily identify differences between bacteriostatic and bactericidal mechanisms and was considerably quicker than the "traditional" methods tested.


Subject(s)
Anti-Infective Agents , Escherichia coli O157 , Artificial Intelligence , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Spectrum Analysis , Machine Learning , Microbial Sensitivity Tests
3.
Ultrasound Obstet Gynecol ; 63(4): 481-488, 2024 04.
Article in English | MEDLINE | ID: mdl-37820067

ABSTRACT

OBJECTIVE: Placental vascular reactivity (PlVR) indicates the ability of the placental vasculature to match blood supply to fetal demand. Many pregnancy disorders alter the characteristics of PlVR, resulting in suboptimal oxygen delivery, although current understanding is limited by the lack of non-invasive, repeatable methods to measure PlVR in utero. Our objective was to quantify PlVR by measuring the placental response to transient changes in maternal carbon dioxide (CO2) using blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI). We hypothesized that PlVR will increase with gestational age to meet the changing demands of a growing fetus, and that PlVR will be driven by a maternal response to changes in CO2 concentration. METHODS: This was a cross-sectional study of 35 women with a healthy singleton pregnancy, of whom 31 were included in the analysis. The median gestational age was 32.6 (range, 22.6-38.4) weeks. Pregnant women were instructed to follow audiovisual breathing cues during a MRI scan. Maternal end-tidal CO2 (EtCO2) was measured concurrently with resting placental BOLD MRI for a total of 7-8 min. Preprocessing of magnetic resonance images consisted of manual delineation of placental anatomy and motion correction. In each placental voxel, vascular reactivity was computed using a coherence-weighted general linear model between MRI signal and EtCO2 stimulus. Global PlVR was computed as the mean of voxel-wise PlVR values across the placenta. RESULTS: PlVR, quantified by the placental response to induced, transient changes in maternal CO2, was consistently measured in utero using BOLD MRI. PlVR increased non-linearly with advancing gestational age (P < 0.001) and was higher on the fetal side of the placenta. PlVR was associated positively with fetal brain volume after accounting for gestational age. PlVR did not show any significant associations with maternal characteristics. CONCLUSIONS: We present, for the first time, a non-invasive paradigm to quantify PlVR in ongoing human pregnancies without the use of exogenous gases or contrast agents. Our findings suggest that PlVR is driven by a fetal response to changes in maternal CO2. Ease of translation to the clinical setting makes PlVR a promising biomarker for the identification and management of high-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Placenta , Pregnancy Complications , Pregnancy , Female , Humans , Infant , Placenta/blood supply , Cross-Sectional Studies , Carbon Dioxide , Magnetic Resonance Imaging/methods , Oxygen
4.
Br J Surg ; 108(10): 1207-1215, 2021 10 23.
Article in English | MEDLINE | ID: mdl-34095952

ABSTRACT

BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.


Subject(s)
Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Aged , Chemoradiotherapy, Adjuvant , Disease-Free Survival , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/surgery , Esophagectomy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Proportional Hazards Models , Salvage Therapy
5.
J Labelled Comp Radiopharm ; 61(7): 533-539, 2018 06 15.
Article in English | MEDLINE | ID: mdl-29493011

ABSTRACT

SCH 430765 and SCH 500496 are potent and selective antagonists of the NPY5 receptor. NPY5 receptor antagonists have the potential for the treatment of obesity. [35 S]SCH 500946 was prepared for a competition binding assay which led to the identification of SCH 430765. Three distinct isotopically labelled forms of SCH 430765 were synthesized. [3 H]SCH 430765 was prepared for a preliminary absorption, distribution, metabolism and excretion data evaluation of the compound and [14 C]SCH 430765 for more definitive absorption, distribution, metabolism and excretion data work. In addition, [13 C2 ,2 H4 ]SCH 430765 was prepared as an internal standard for a LC-MS bioanalytical method. The paper discusses the synthesis of 3 isotopically labelled forms of SCH 430765 and [35 S]SCH 500946.


Subject(s)
Piperidines/chemical synthesis , Piperidines/pharmacology , Receptors, Neuropeptide Y/antagonists & inhibitors , Carbon Isotopes , Carbon Radioisotopes , Chemistry Techniques, Synthetic , Isotope Labeling , Piperidines/chemistry , Radiochemistry , Sulfur Radioisotopes , Tritium
6.
Nano Lett ; 17(4): 2159-2164, 2017 04 12.
Article in English | MEDLINE | ID: mdl-28249115

ABSTRACT

This Letter reports on the unusual diffusion behavior of Ge during oxidation of a multilayer Si/SiGe fin. It is observed that oxidation surprisingly results in the formation of vertically stacked Si nanowires encapsulated in defect free epitaxial strained SixGe1-x. High angle annular dark field scanning transmission electron microscopy (HAADF-STEM) shows that extremely enhanced diffusion of Ge occurs along the vertical Si/SiO2 oxidizing interface and is responsible for the encapsulation process. Further oxidation fully encapsulates the Si layers in defect free single crystal SixGe1-x (x up to 0.53), which results in Si nanowires with up to -2% strain. Atom probe tomography reconstructions demonstrate that the resultant nanowires run the length of the fin. We found that the oxidation temperature plays a significant role in the formation of the Si nanowires. In the process range of 800-900 °C, pure strained and rounded Si nanowires down to 2 nm in diameter can be fabricated. At lower temperatures, the Ge diffusion along the oxidizing Si/SiO2 interface is slow, and rounding of the nanowire does not occur, while at higher temperatures, the diffusivity of Ge into Si is sufficient to result in dilution of the pure Si nanowire with Ge. The use of highly selective etchants to remove the SiGe could provide a new pathway for the creation of highly controlled vertically stacked nanowires for gate all around transistors.

7.
Ultrasound Obstet Gynecol ; 50(2): 156-166, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27935148

ABSTRACT

OBJECTIVE: To compare the effectiveness of customized vs population-based growth charts for the prediction of adverse pregnancy outcomes. METHODS: MEDLINE, ClinicalTrials.gov and The Cochrane Library were searched up to 31 May 2016 to identify interventional and observational studies comparing adverse outcomes among large- (LGA) and small- (SGA) for-gestational-age neonates, when classified according to customized vs population-based growth charts. Perinatal mortality and admission to the neonatal intensive care unit (NICU) of both SGA and LGA neonates, intrauterine fetal demise (IUFD) and neonatal mortality of SGA neonates, and neonatal shoulder dystocia and hypoglycemia as well as maternal third- and fourth-degree perineal lacerations in LGA pregnancies were evaluated. RESULTS: The electronic search identified 237 records that were examined based on title and abstract, of which 27 full-text articles were examined for eligibility. After excluding seven articles, 20 observational studies were included in a Bayesian meta-analysis. Neonates classified as SGA according to customized growth charts had higher risks of IUFD (odds ratio (OR), 7.8 (95% CI, 4.2-12.3)), neonatal death (OR, 3.5 (95% CI, 1.1-8.0)), perinatal death (OR, 5.8 (95% CI, 3.8-7.8)) and NICU admission (OR, 3.6 (95% CI, 2.0-5.5)) than did non-SGA cases. Neonates classified as SGA according to population-based growth charts also had increased risk for adverse outcomes, albeit the point estimates of the pooled ORs were smaller: IUFD (OR, 3.3 (95% CI, 1.9-5.0)), neonatal death (OR, 2.9 (95% CI, 1.2-4.5)), perinatal death (OR, 4.0 (95% CI, 2.8-5.1)) and NICU admission (OR, 2.4 (95% CI, 1.7-3.2)). For LGA vs non-LGA, there were no differences in pooled ORs for perinatal death, NICU admission, hypoglycemia and maternal third- and fourth-degree perineal lacerations when classified according to either the customized or the population-based approach. In contrast, both approaches indicated that LGA neonates are at increased risk for shoulder dystocia than are non-LGA ones (OR, 7.4 (95% CI, 4.9-9.8) using customized charts; OR, 8.0 (95% CI, 5.3-10.1) using population-based charts). CONCLUSIONS: Both customized and population-based growth charts can identify SGA neonates at risk for adverse outcomes. Although the point estimates of the pooled ORs may differ for some outcomes, the overlapping CIs and lack of direct comparisons prevent conclusions from being drawn on the superiority of one method. Future clinical trials should compare directly the two approaches in the management of fetuses of abnormal size. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Birth Weight , Growth Charts , Infant, Small for Gestational Age/growth & development , Bayes Theorem , Female , Fetal Macrosomia , Humans , Infant , Infant Mortality , Infant, Newborn , Pregnancy , Pregnancy Outcome
8.
BMC Womens Health ; 17(1): 44, 2017 06 17.
Article in English | MEDLINE | ID: mdl-28623904

ABSTRACT

BACKGROUND: Micronutrient malnutrition has been associated with maternal depressive symptoms (MDS), but little is known about the effects of preconceptional micronutrient supplementation. This paper examined the effects of preconceptional micronutrient supplementation on MDS during pregnancy and postpartum. METHODS: We used data from a double-blind controlled trial (PRECONCEPT) in which 5011 Vietnamese women were randomized to receive weekly supplements containing either a) multiple micronutrients (MM) b) iron and folic acid (IFA) or c) folic acid (FA) until conception (n = 1813). Maternal mental health was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline (preconception), and the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and 3 months postpartum. Elevated MDS was defined as EPDS score ≥ 4. All group comparisons were done using ANOVA or chi-square tests of proportions intention to treat and per protocol analyses (women consumed supplements ≥26 weeks before conception). We also conducted stratified analyses by preconception CES-D scores, underweight, or anemia status using generalized linear models. RESULTS: Baseline CES-D scores were similar across treatment groups. The proportion of women experiencing elevated MDS was 11.3, 8.1 and 4.9% at first, second and third trimesters of pregnancy, respectively, and 3.6% at 3 mo postpartum. Mean EPDS scores at first (1.5 ± 2.7), second (1.1 ± 2.4), and third trimester of pregnancy (0.7 ± 2.0) and early postpartum (0.6 ± 1.8) were low and did not differ by treatment group. However, among women in the highest tertile of CES-D scores at preconception, mean EPDS scores in the first and second trimesters of pregnancy were lower in the MM and IFA groups compared to FA only (P < 0.05). CONCLUSIONS: Weekly preconceptional micronutrient supplements containing iron did not improve depression measures relative to folic acid alone among all women, but may have benefitted women who were at risk for depression. TRIAL REGISTRATION: The trial was registered retrospectively at ClinicalTrials.Gov as NCT01665378 on August 13, 2012.


Subject(s)
Dietary Supplements , Micronutrients/administration & dosage , Postpartum Period/psychology , Preconception Care/methods , Pregnancy Complications/psychology , Adolescent , Adult , Double-Blind Method , Female , Folic Acid/administration & dosage , Humans , Pregnancy , Treatment Outcome , Vietnam , Vitamin B Complex/administration & dosage , Young Adult
9.
BMC Public Health ; 17(1): 452, 2017 05 16.
Article in English | MEDLINE | ID: mdl-28511688

ABSTRACT

BACKGROUND: Poor adherence to micronutrient supplementation often limits the effectiveness of public health programs. While predictors of adherence to micronutrient supplementation during pregnancy are well documented, information on adherence to preconception supplements is scarce. The objective of this study was to describe the predictors of adherence to preconception and prenatal micronutrient supplementation among women participating in a randomized control trial in Vietnam. METHODS: Adherence data were collected prospectively from a double blind randomized controlled trial in rural Vietnam. Five thousand eleven women of reproductive age were randomized to receive preconception supplements for weekly consumption containing either: Folic Acid, Iron and Folic Acid (IFA), or Multiple Micronutrients. Women who became pregnant received prenatal IFA supplements for daily consumption through delivery. Village health workers visited participants' homes every two weeks to deliver supplements and record consumption and side effects. Multivariate logistic regression was used to assess individual, household, and programmatic predictors of supplement adherence. RESULTS: Adherence was high with 78 and 82% of the women consuming more than 80% of the preconception and prenatal supplements, respectively. Women of minority ethnicity (OR = 0.78 95% CI = 0.67, 0.91) and farmers (OR = 0.71 95% CI = 0.58, 0.88) were less likely to consume >80% of the preconception supplements while socioeconomic status (SES) (OR = 2.71 highest vs. lowest quintile; 95% CI = 2.10, 3.52) was positively associated with >80% adherence in the entire preconception sample with available information (n = 4417). Women in their first pregnancy had lower prenatal adherence compared to multiparous women. At the programmatic level, each village health worker visit was associated with higher odds of >80% adherence by 3-5% before pregnancy and 18% during pregnancy. CONCLUSIONS: Key determinants of adherence included SES, ethnicity, occupation (farmer) and parity which may be helpful for targeting women for counseling on supplement adherence. Increased contact with village health workers was positively associated with adherence to micronutrient supplementation both before conception and during pregnancy indicating the need for resources to support community outreach to women of reproductive age. TRIAL REGISTRATION: NCT01665378 . Registered on August 12, 2012.


Subject(s)
Dietary Supplements/statistics & numerical data , Medication Adherence/statistics & numerical data , Micronutrients/administration & dosage , Adult , Double-Blind Method , Female , Folic Acid/administration & dosage , Humans , Iron/administration & dosage , Micronutrients/therapeutic use , Parity , Pregnancy , Prospective Studies , Rural Population , Socioeconomic Factors , Vietnam
10.
J Labelled Comp Radiopharm ; 60(4): 194-199, 2017 04.
Article in English | MEDLINE | ID: mdl-28129428

ABSTRACT

MK 3814 is a potent and selective antagonist of the A2a receptor. A2a receptor antagonists have the potential for the treatment of Parkinson disease. Three distinct isotopically labelled forms of MK 3814 were synthesized. [3 H]MK 3814 was prepared for a preliminary absorption, distribution, metabolism, and excretion data (ADME) evaluation of the compound and [14 C]MK 3814 for more definitive ADME work, including an absorption, metabolism, and excretion study in man. In addition, [2 H4 ]MK 3814 was prepared as an internal standard for a liquid chromatography mass spectrometry bioanalytical method. This paper discusses the synthesis of 3 isotopically labelled forms of MK 3814.


Subject(s)
Carbon Radioisotopes/chemistry , Deuterium/chemistry , Pyrimidines/chemistry , Pyrimidines/chemical synthesis , Triazoles/chemistry , Triazoles/chemical synthesis , Tritium/chemistry , Chemistry Techniques, Synthetic , Isotope Labeling
11.
J Nutr ; 146(7): 1445S-52S, 2016 07.
Article in English | MEDLINE | ID: mdl-27281806

ABSTRACT

BACKGROUND: Maternal nutritional status before and during early pregnancy plays a critical role in fetal growth and development. The benefits of periconception folic acid (FA) supplementation in the prevention of neural tube defects is well recognized, but the evidence for preconception micronutrient interventions for improving pregnancy outcomes is limited. OBJECTIVE: This study aimed to evaluate whether preconception supplementation with weekly iron and folic acid (IFA) or multiple micronutrients (MMs) improves birth outcomes compared with FA alone. METHODS: We recruited 5011 women of reproductive age in a double-blind, randomized controlled trial in Vietnam and provided weekly supplements containing either 2800 µg FA, 60 mg Fe and 2800 µg FA (IFA), or the same amount of FA and iron plus other MMs until they conceived (n = 1813). All pregnant women received daily IFA through delivery, and were followed up for birth outcomes, including birth weight, gestational age, preterm delivery and small for gestational age (SGA). Group comparisons were done with the use of ANOVA or chi-square tests for both intention-to-treat (n = 1599) and per-protocol analyses (women consumed supplements ≥26 wk before conception; n = 824). Effect modification by baseline underweight or anemia status was tested with the use of generalized linear models. RESULTS: The mean age of the women was 26 y, 30% were underweight, and <10% were nulliparous. The groups were similar for most baseline characteristics. The mean ± SD duration of the preconception intervention was 33 ± 25 wk and compliance was high (>90%). Infants born to the 3 groups of women did not differ (P ≥ 0.05) on mean ± SD birth weight (3076.8 ± 444.5 g) or gestational age (39.2 ± 2.0 wk), or prevalence of SGA (12%), low birth weight (5%) and preterm delivery (10%). There were no significant differences in women who consumed supplements ≥26 wk before conception or by baseline underweight or anemia. CONCLUSION: Weekly supplementation with MMs or IFA before conception did not affect birth outcomes compared with FA in rural Vietnamese women. The trial was registered at clinicaltrials.gov as NCT01665378.


Subject(s)
Folic Acid/administration & dosage , Iron/administration & dosage , Micronutrients/administration & dosage , Adolescent , Adult , Anemia/prevention & control , Birth Weight , Body Composition , Drug Therapy, Combination , Female , Gestational Age , Humans , Infant, Newborn , Pregnancy , Rural Population , Vietnam , Young Adult
12.
Paediatr Perinat Epidemiol ; 30(3): 256-66, 2016 May.
Article in English | MEDLINE | ID: mdl-26848715

ABSTRACT

BACKGROUND: Small for gestational age (SGA) is a global health problem. Identifying the timing of fetal growth faltering is critical for developing preventive interventions. We aim to describe patterns of fetal growth and to predict SGA at birth using fetal ultrasound measurements. METHODS: We studied 1412 pregnant women enrolled in a randomised-controlled trial evaluating maternal micronutrient supplementation in Thai Nguyen province, Vietnam. Ultrasound examinations included biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC), and femur length (FL). Measures were assessed using the new international fetal growth standards (INTERGROWTH-21st Project). Generalised linear mixed logit regression models were used to examine the association between ultrasound measures and SGA at birth. RESULTS: Overall fetal growth restriction began in early pregnancy and continued through delivery, but the timing of growth faltering varied by measure: it began by 20 weeks for HC, BPD and AC, earlier as compared to FL growth that started >30 weeks. SGA infants had significantly lower mean fetal growth parameters as early as 14 weeks. Ultrasound measures below the 10th percentile were associated with a two to four times higher risk of SGA at birth compared to fetuses greater than the 50th percentile, with the largest odds ratios for AC (OR 3.9, 95% confidence interval (CI) 2.7, 5.7). CONCLUSIONS: Fetal growth faltering by ultrasound begins in early gestation among rural Vietnamese populations; these patterns clearly identified those to be born SGA. Efforts to prevent fetal growth faltering must begin early in pregnancy and perhaps even before pregnancy.


Subject(s)
Fetal Growth Retardation/diagnostic imaging , Infant, Small for Gestational Age/blood , Micronutrients/therapeutic use , Pregnant Women , Ultrasonography, Prenatal , Adult , Birth Weight , Dietary Supplements , Female , Fetal Growth Retardation/etiology , Fetal Growth Retardation/prevention & control , Gestational Age , Humans , Infant, Newborn , Maternal Nutritional Physiological Phenomena , Pregnancy , Prospective Studies , Rural Population , Treatment Outcome , Vietnam/epidemiology
13.
Nanotechnology ; 27(36): 365301, 2016 Sep 09.
Article in English | MEDLINE | ID: mdl-27479353

ABSTRACT

The advancement of trapping and detection of nano-objects at very low laser powers in the near-infra-red region (NIR) is crucial for many applications. Singular visible-light nano-optics based on abrupt phase changes have recently demonstrated a significant improvement in molecule detection. Here, we propose and demonstrate tunable plasmonic nanodevices, which can improve both the trapping field enhancement and detection of nano-objects using singular phase drops in the NIR range. The plasmonic nanostructures, which consist of gaps with dimensions 50 nm × 50 nm connecting nanorings in arrays is discussed. These gaps act as individual detection and trapping sites. The tunability of the system is evident from extinction and reflection spectra while increasing the aperture size in the arrays. Additionally, in the region where the plasmonic nano-array exhibits topologically-protected, near-zero reflection behaviour, the phase displays a rapid change. Our experimental data predict that, using this abrupt phase changes, one can improve the detection sensitivity by 10 times compared to the extinction spectra method. We finally report experimental evidence of 100 nm polystyrene beads trapping using low incident power on these devices. The overall design demonstrates strong capability as an optical, label-free, non-destructive tool for single molecule manipulation where low trapping intensity, minimal photo bleaching and high sensitivity is required.

15.
J Labelled Comp Radiopharm ; 59(5): 190-6, 2016 May 15.
Article in English | MEDLINE | ID: mdl-26991320

ABSTRACT

Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. CCR5 receptor antagonists have the potential for the treatment of HIV infections. Four distinct isotopically labelled forms of SCH 417690 were synthesized. Low specific activity [(3) H]SCH 417690 was prepared for a preliminary absorption, distribution, metabolism and excretion evaluation of the compound and [(14) C]SCH 417690 for more definitive absorption, distribution, metabolism and excretion work, including an absorption, metabolism and excretion study in man. In addition, high specific activity [(3) H]SCH 417690 was prepared for CCR5 receptor binding work and [(2) H4 ]SCH 417690 was prepared as an internal standard for a liquid chromatography-mass spectrometry bioanalytical method. The paper discusses the synthesis of four isotopically labelled forms of SCH 417690.


Subject(s)
Carbon Radioisotopes/chemistry , Piperazines/chemistry , Piperazines/chemical synthesis , Pyrimidines/chemistry , Pyrimidines/chemical synthesis , Tritium/chemistry , Chemistry Techniques, Synthetic , Isotope Labeling
16.
Nat Genet ; 38(2): 234-9, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16415889

ABSTRACT

Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation.


Subject(s)
Databases, Genetic , Disease Models, Animal , Genomics , Heart Diseases/genetics , Hematologic Diseases/genetics , Lung Diseases/genetics , Animals , Gene Expression Profiling , Genetic Variation , Genomics/methods , Heart Diseases/physiopathology , Hematologic Diseases/physiopathology , Hypoxia/chemically induced , Internet , Lung Diseases/physiopathology , Male , Microarray Analysis , Myocardium/metabolism , Rats , Rats, Inbred BN , Rats, Inbred Dahl , Regulatory Sequences, Nucleic Acid/genetics
17.
BMC Genomics ; 15: 96, 2014 Feb 04.
Article in English | MEDLINE | ID: mdl-24495417

ABSTRACT

BACKGROUND: The introduction of benchtop sequencers has made adoption of whole genome sequencing possible for a broader community of researchers than ever before. Concurrently, metagenomic sequencing (MGS) is rapidly emerging as a tool for interrogating complex samples that defy conventional analyses. In addition, next-generation sequencers are increasingly being used in clinical or related settings, for instance to track outbreaks. However, information regarding the analytical sensitivity or limit of detection (LoD) of benchtop sequencers is currently lacking. Furthermore, the specificity of sequence information at or near the LoD is unknown. RESULTS: In the present study, we assess the ability of three next-generation sequencing platforms to identify a pathogen (viral or bacterial) present in low titers in a clinically relevant sample (blood). Our results indicate that the Roche-454 Titanium platform is capable of detecting Dengue virus at titers as low as 1X102.5 pfu/mL, corresponding to an estimated 5.4X104 genome copies/ml maximum. The increased throughput of the benchtop sequencers, the Ion Torrent PGM and Illumina MiSeq platforms, enabled detection of viral genomes at concentrations as low as 1X104 genome copies/mL. Platform-specific biases were evident in sequence read distributions as well as viral genome coverage. For bacterial samples, only the MiSeq platform was able to provide sequencing reads that could be unambiguously classified as originating from Bacillus anthracis. CONCLUSION: The analytical sensitivity of all three platforms approaches that of standard qPCR assays. Although all platforms were able to detect pathogens at the levels tested, there were several noteworthy differences. The Roche-454 Titanium platform produced consistently longer reads, even when compared with the latest chemistry updates for the PGM platform. The MiSeq platform produced consistently greater depth and breadth of coverage, while the Ion Torrent was unequaled for speed of sequencing. None of the platforms were able to verify a single nucleotide polymorphism responsible for antiviral resistance in an Influenza A strain isolated from the 2009 H1N1 pandemic. Overall, the benchtop platforms perform well for identification of pathogens from a representative clinical sample. However, unlike identification, characterization of pathogens is likely to require higher titers, multiple libraries and/or multiple sequencing runs.


Subject(s)
High-Throughput Nucleotide Sequencing/instrumentation , Bacillus anthracis/genetics , Chromosome Mapping , Computational Biology , DNA, Bacterial/blood , Databases, Genetic , Dengue Virus/genetics , Genome, Viral , High-Throughput Nucleotide Sequencing/standards , Humans , Influenza A Virus, H1N1 Subtype/genetics , RNA, Viral/blood
18.
Clin Chem ; 60(5): 758-64, 2014 May.
Article in English | MEDLINE | ID: mdl-24568795

ABSTRACT

BACKGROUND: Reference intervals of high-sensitivity troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been determined from Western populations. No data are available regarding expected values in Asian populations. METHODS: A total of 1157 age- and sex-matched healthy individuals (mean age, 41.2 years; 48.0% male) were prospectively enrolled from the US (n = 565) and Vietnam (n = 592). Blood samples were analyzed for hs-cTnT and NT-proBNP. Median values were determined for each country and compared in unadjusted analyses and in analyses adjusted for age, sex, body mass index, study site, race, and vital signs. RESULTS: Median hs-cTnT concentrations were slightly higher for individuals from the US than for those from Vietnam, but both were below the limit of detection (3.7 vs 3.0 ng/L, respectively; P = 0.03). More US participants had an hs-cTnT concentration above the limit of detection (57.2% vs 47.3%; P = 0.001), but the 99th percentile concentration was slightly higher for Asians (US 15.1 vs Vietnam 19.0 ng/L). Concentrations for >98% of both populations were below the standard hs-cTnT 99th percentile of 14.0 ng/L (P = 0.54). Median NT-proBNP concentrations were slightly higher for US participants compared with Vietnamese participants (28 vs 16 ng/L, respectively; P < 0.001). Following adjustment, differences in concentrations of NT-proBNP between healthy US and Vietnamese populations remained significant, whereas for hs-cTnT the differences were no longer significant. Inclusion of hs-cTnT values down to the limit of blank did not change the result. CONCLUSIONS: The differences in hs-cTnT and NT-proBNP between healthy individuals from the US and Vietnam are small. Previously derived reference intervals for both analytes may be applied in Asian populations.


Subject(s)
Heart Failure/blood , Myocardial Infarction/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin T/blood , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , Cross-Sectional Studies , Female , Heart Failure/ethnology , Humans , Limit of Detection , Male , Middle Aged , Myocardial Infarction/ethnology , Predictive Value of Tests , Prospective Studies , Reference Values , Sex Factors , United States , Vietnam , Young Adult
19.
Opt Express ; 22(13): 16322-34, 2014 Jun 30.
Article in English | MEDLINE | ID: mdl-24977883

ABSTRACT

The evanescent field of an optical nanofiber presents a versatile interface for the manipulation of micron-scale particles in dispersion. Here, we present a detailed study of the optical binding interactions of a pair of 3.13 µm SiO(2) spheres in the nanofiber evanescent field. Preferred equilibrium positions for the spheres as a function of nanofiber diameter and sphere size are discussed. We demonstrated optical propulsion and self-arrangement of chains of one to seven 3.13 µm SiO(2) particles; this effect is associated with optical binding via simulated trends of multiple scattering effects. Incorporating an optical nanofiber into an optical tweezers setup facilitated the individual and collective introduction of selected particles to the nanofiber evanescent field for experiments. Computational simulations provide insight into the dynamics behind the observed behavior.

20.
Nutr J ; 12: 126, 2013 Sep 12.
Article in English | MEDLINE | ID: mdl-24028650

ABSTRACT

BACKGROUND AND OBJECTIVES: Adequate nutrient intakes among women of reproductive age (WRA) are important determinants of maternal, neonatal and child health outcomes. However, data on dietary intake for WRA in Vietnam are lacking. This paper aimed to examine the adequacy and determinants of energy and macronutrient intakes among WRA enrolled in a study of preconceptual micronutrient supplementation (PRECONCEPT) being conducted in 20 rural communes in Thai Nguyen province, Vietnam. METHODS: Dietary intakes were determined for 4983 WRA who participated in the baseline survey using a previously validated 107-item (semi-quantitative) food-frequency questionnaire that was administered by trained field workers. Multivariate linear and logistic regression analyses were used to examine factors associated with energy and macronutrient intakes. RESULTS: A disproportionate number of energy came from starches, primarily rice. Carbohydrate, fat and protein constituted 65.6%, 19.5% and 14.8% of total energy, respectively. Fat intake was below recommended levels in 56.5% of respondents, but carbohydrate intakes were above recommended level in 54.6%. Only 0.1% and 5.2% of WRA achieved adequate intake of n-3 and n-6 long-chain polyunsaturated fatty acids, respectively. Multivariate linear regression revealed that low education, low socioeconomic status, and food insecurity were significant predictors of reduced total energy intake, reduced energy from protein and fat, and greater energy from carbohydrates. Logistic regression confirmed that inadequate macronutrient intake was more common among the poor, food insecure, and less educated. CONCLUSIONS: Imbalanced dietary intakes among underprivileged women reflect lack of dietary diversity. Nutrition programs should be linked with social development, poverty reduction, education programs and behavior change counseling in order to improve the nutritional status of WRA in Vietnam.


Subject(s)
Diet/adverse effects , Malnutrition/etiology , Nutritional Status , Rural Health , Adolescent , Adult , Diet/ethnology , Diet/psychology , Diet Surveys , Energy Intake/ethnology , Family Characteristics/ethnology , Female , Food Supply/economics , Health Promotion , Humans , Malnutrition/economics , Malnutrition/epidemiology , Malnutrition/ethnology , Nutrition Policy , Nutritional Status/ethnology , Oryza/chemistry , Patient Compliance/ethnology , Rural Health/economics , Rural Health/ethnology , Seeds/chemistry , Socioeconomic Factors , Vietnam/epidemiology , Young Adult
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