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1.
Nature ; 571(7766): 541-545, 2019 07.
Article in English | MEDLINE | ID: mdl-31341304

ABSTRACT

Although the possibility of spatial variations in the superfluid of unconventional, strongly correlated superconductors has been suggested1-7, it is not known whether such inhomogeneities-if they exist-are driven by disorder, strong scattering or other factors. Here we use atomic-resolution Josephson scanning tunnelling microscopy to reveal a strongly inhomogeneous superfluid in the iron-based superconductor FeTe0.55Se0.45. By simultaneously measuring the topographic and electronic properties of the superconductor, we find that this inhomogeneity in the superfluid is not caused by structural disorder or strong inter-pocket scattering and is not correlated with variations in the energy required to break electron pairs. Instead, we see a clear spatial correlation between the superfluid density and the quasiparticle strength (the height of the coherence peak) on a local scale. This result places iron-based superconductors on equal footing with copper oxide superconductors, where a similar relation has been observed on the macroscopic scale. Our results establish the existence of strongly inhomogeneous superfluids in unconventional superconductors, excluding chemical disorder and inter-band scattering as the causes of the inhomogeneity, and shed light on the relation between quasiparticle character and superfluid density. When repeated at different temperatures, our technique could further help to elucidate what local and global mechanisms limit the critical temperature in unconventional superconductors.

2.
Pediatr Surg Int ; 39(1): 262, 2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37668756

ABSTRACT

INTRODUCTION: Central venous catheter (CVC) placement is commonly performed in children. We aim to develop simple formulas to predict CVC intravascular length to minimise radiation exposure associated with the procedure. METHODS: 124 paediatric patients who received tunnelled neck CVCs and subsequent CT thorax at Hong Kong Children's Hospital from January 2020 to July 2022 were reviewed retrospectively. Formula development cohorts were subdivided by insertion sites-9 right external jugular vein (REJV), 41 right internal jugular vein (RIJV), 14 left external jugular vein (LEJV), 10 left internal jugular vein (LIJV). Using measurements from CT by two radiologists, formulas predicting the CVC intravascular length based on height and insertion sites were developed using a linear regression model. These formulas were tested with validation cohorts (10 randomly selected cases in REJV and RIJV groups respectively). Validation cohorts were not available for LEJV and LIJV groups due to small sample sizes. RESULT: The goodness-of-fit (R^2) of all formulas are above 0.8. In the validation cohorts, the REJV formula was predictive of intravascular CVC length within 1 cm in 70% of CVC with mean absolute difference of 0.63 cm (SD 0.48 cm), and the RIJV formula was predictive of intravascular CVC length within 1 cm in 80% of CVC with mean absolute difference of 0.67 cm (SD 0.53 cm). CONCLUSION: Intravascular CVC length can be estimated using simple formulas based on height and insertion sites. Further prospective validation of the LEJV and LIJV formulas is needed.


Subject(s)
Central Venous Catheters , Humans , Child , Retrospective Studies , Brachiocephalic Veins , Hospitals, Pediatric , Jugular Veins/diagnostic imaging
3.
Adv Exp Med Biol ; 1269: 51-55, 2021.
Article in English | MEDLINE | ID: mdl-33966194

ABSTRACT

A new device designed to scan oxygen partial pressure along a line in a biological tissue is described in this paper. The probe is housed in a stainless-steel needle. As opposed to other devices for oxygen scanning in tissue, the new probe does not require mechanical translation of the needle in the tissue. The probe includes an active sensing area along the needle shaft that can be scanned optically by an internal optical fiber. This feature allows for repeated scans of tissue oxygen along a line without translating the needle with respect to the tissue, thus avoiding tissue damage associated with needle motion. First, we describe the design of the device including its sensing mechanism, mechanical design, optical configuration, and signal processing. We then move on to describe the results of the device characterization and testing. Finally, we conclude by discussing possible applications of the device in research and in clinical diagnoses and treatment monitoring.


Subject(s)
Needles , Oxygen , Signal Processing, Computer-Assisted
4.
Niger J Clin Pract ; 24(6): 795-801, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34121724

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV) infection is a major global health problem, and healthcare workers (HCWs) are at high risk for HBV infection. Current guidelines strongly recommend immunization and screening for high-risk groups. AIMS: We evaluated immunization and screening for HBV vaccination, assessed post-vaccination immune status of HCW's and characterized potential risk factors associated with poor immune response. MATERIALS AND METHODS: From January 2010 to December 2018, we retrospectively analyzed comprehensive health checkup data for a total of 303 HCWs who received an HBV vaccination. After vaccination, HBV surface antibody (anti-HBs) titers were collected and the distribution of immune response types was determined. Risk factors for poor immune responses were identified using logistic regression. RESULTS: A total of 213 HCWs were analyzed after exclusion based on the exclusion criteria. In total, 28 (13.2%) HCWs had anti-HBs titers <100 mIU/mL (hyporesponsive/nonresponsive groups), and 185 (86.8%) had anti-HBs titers ≥100 mIU/mL (hyperresponsive group). Follow-up observations found that 75% (21/28) of the hyporesponsive/nonresponsive groups did not have increased anti-HBs titers or did not maintain an increased response. A multivariate analysis showed that HBV antibody titers at the time of employment were a significant risk factor (OR, 6.12; CI, 1.34-27.93; P = 0.019). CONCLUSIONS: More attention should be paid to groups that are hyporesponsive/nonresponsive after vaccination and to those with low anti-HBs titers at the beginning of employment. HCWs can be further protected from HBV if their results are discussed at postvaccination follow-ups.


Subject(s)
Hepatitis B Surface Antigens , Hepatitis B , Health Personnel , Hepatitis B/prevention & control , Hepatitis B Antibodies , Hepatitis B Vaccines , Humans , Immunity , Retrospective Studies , Vaccination
5.
Phys Rev Lett ; 122(13): 133201, 2019 Apr 05.
Article in English | MEDLINE | ID: mdl-31012628

ABSTRACT

We demonstrate gate operations on a single qubit at a specific site without perturbing the coherence of an adjacent qubit in a 1D optical lattice when the site separation is only 532 nm. Three types of spin rotations are performed on the target qubit with fidelities between 0.88±0.05 and 0.99±0.01, whereas the superposition state of the adjacent one is preserved with fidelities between 0.93±0.04 and 0.97±0.04. The qubit is realized by a pair of Zeeman-sensitive ground hyperfine states of a ^{7}Li atom, and each site is identified by its resonance frequency in a magnetic field gradient of 1.6 G/cm. We achieve the site-specific resolving power in the frequency domain by using magic polarization for the lattice beam that allows a Fourier-limited transition linewidth as well as by highly stabilizing the lattice parameters and the ambient conditions. We also discuss a two-atom entanglement scheme using a blockade by cold collisional shifts in a 1D superlattice, for which a coherent manipulation of individual qubits is a prerequisite.

6.
Nutr Metab Cardiovasc Dis ; 29(4): 360-366, 2019 04.
Article in English | MEDLINE | ID: mdl-30782509

ABSTRACT

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is a cluster of multiple risk factors including central obesity that may lead to cardiac damage and cardiovascular events. We investigated whether visceral obesity induces cardiac structural and functional remodeling independently from central obesity and other risk factors in subjects with suspected MetS. METHODS AND RESULTS: We studied 229 participants with suspected MetS. Visceral fat area (VFA) was measured by bioelectrical impedance analysis. Left ventricular (LV) mass index, early diastolic velocity of mitral annulus (e'), and LV global longitudinal strain (GLS) were measured by echocardiography. Subjects were categorized into high and low VFA group (VFAh and VFAl). MetS was more prevalent in the VFAh than in the VFAl (p = 0.004). The VFAh had a higher waist circumference (WC) than the VFAl (p < 0.001). LV mass index was higher, but e' and GLS were lower in the VFAh than in VFAl (all p < 0.05). VFA was well correlated with blood pressure, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein and adiponectin (all p < 0.05). VFA was correlated to LV mass index, e', and GLS (all p < 0.05) and was independently associated with GLS after adjustment for other risk factors, including WC (p = 0.005). CONCLUSIONS: Visceral obesity assessed by VFA was well correlated with parameters of MetS. Visceral obesity, but not central obesity measured by WC, was independently associated with structural and functional cardiac remodeling in subjects with suspected MetS. It suggests that visceral obesity should be considered as an important risk factor for cardiac damage in dysmetabolic subjects. TRIAL REGISTRATION: NCT02077530 (date of registration: November 1, 2013).


Subject(s)
Abdominal Fat/physiopathology , Adiposity , Cardiovascular Diseases/physiopathology , Intra-Abdominal Fat/physiopathology , Metabolic Syndrome/physiopathology , Obesity, Abdominal/physiopathology , Ventricular Function, Left , Ventricular Remodeling , Abdominal Fat/diagnostic imaging , Abdominal Fat/metabolism , Biomarkers/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnostic imaging , Echocardiography, Doppler, Pulsed , Electric Impedance , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/metabolism , Male , Metabolic Syndrome/blood , Metabolic Syndrome/diagnostic imaging , Middle Aged , Obesity, Abdominal/blood , Obesity, Abdominal/diagnostic imaging , Prognosis , Prospective Studies , Risk Factors , Tomography, X-Ray Computed , Waist Circumference
7.
Article in English | MEDLINE | ID: mdl-28940854

ABSTRACT

Cancer survivors engage in suboptimal levels of health behaviours and report many barriers to health behaviours, but we lack a solid understanding of the different levels of barriers and how they relate to enacted health behaviours. To address these issues, we conducted mixed-method research in 97 breast cancer survivors. Participants' barriers to physical activity (PA) and healthy diet, asked as an open-ended question, were coded as individual-level, social-level, and organisational/environmental-level for each health behaviour. Moderate-to-vigorous PA and fruit and vegetable (F&V) intake were assessed. Most participants perceived at least one PA (72.7%) and diet (64.9%) individual-level barrier (e.g. physical symptoms/injury); only 15.2% (PA) and 15.6% (diet) reported at least one social-level barrier (e.g. family obligations). About 28.8% (PA) and 29.9% (diet) perceived at least one organisational/environmental-level barrier (e.g. job demand, cost of F&V). Survivors perceiving individual-level dietary barriers consumed less F&V (-.65 servings/day) than those not perceiving dietary barriers at this level. Survivors perceiving social-level dietary barriers reported marginally lower F&V intake (-.65 servings/day) than their counterparts. Those perceiving organisational/environmental-level PA barriers reported marginally fewer minutes (-44.30/week) of moderate-to-vigorous PA than their counterparts. Barriers at multiple levels should be addressed to improve health behaviours among breast cancer survivors.


Subject(s)
Breast Neoplasms , Cancer Survivors , Diet, Healthy , Exercise , Health Behavior , Adult , Aged , Aged, 80 and over , Diet , Female , Fruit , Humans , Middle Aged , Multilevel Analysis , Qualitative Research , Surveys and Questionnaires , Vegetables
9.
Opt Express ; 24(19): 21910-20, 2016 Sep 19.
Article in English | MEDLINE | ID: mdl-27661926

ABSTRACT

We report on measurement of small displacements with sub-nanometer precision using an optoelectronic oscillator (OEO) with an intra-loop Michelson interferometer. In comparison with conventional homodyne and heterodyne detection methods, where displacement appears as a power change or a phase shift, respectively, in the OEO detection, the displacement produces a shift in the oscillation frequency. In comparison with typical OEO sensors, where the frequency shift is proportional to the OEO oscillation frequency in radio-frequency domain, the frequency shift in our method with an intra-loop interferometer is proportional to an optical frequency. We constructed a hybrid apparatus and compared characteristics of the OEO and heterodyne detection methods.

10.
Diabet Med ; 33(12): 1649-1654, 2016 12.
Article in English | MEDLINE | ID: mdl-27100138

ABSTRACT

AIM: To assess the relationship between plasma neutrophil gelatinase-associated lipocalin (NGAL) levels and diabetic retinopathy in patients with Type 2 diabetes. METHODS: In total, 204 patients with Type 2 diabetes were investigated in this cross-sectional study. They were classified as having no diabetic retinopathy, non-proliferative diabetic retinopathy (NPDR) or proliferative retinopathy (PDR), according to the degree of diabetic retinopathy. Thus, diabetic retinopathy in the patients in this study was either NPDR or PDR. RESULTS: Plasma NGAL concentrations were significantly higher in patients with diabetic retinopathy than in those without. The mean plasma NGAL levels differed significantly according to the severity of diabetic retinopathy (no diabetic retinopathy, 120.8 ng/ml; NPDR, 217.8 ng/ml; PDR, 372.4 ng/ml; P for trend = 0.002) after adjustment for other covariates. In multivariable analysis, plasma NGAL levels were significantly associated with diabetic retinopathy (odds ratio for each standard deviation increase in the logarithmic value, 7.75; 95% confidence interval, 2.04-29.41, P = 0.003). CONCLUSION: Plasma NGAL levels were positively associated with diabetic retinopathy in patients with Type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2/etiology , Diabetic Retinopathy/etiology , Lipocalin-2/physiology , Aged , Analysis of Variance , Biomarkers/metabolism , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetic Retinopathy/blood , Female , Humans , Lipocalin-2/metabolism , Male , Middle Aged
11.
Vox Sang ; 111(4): 425-430, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27864976

ABSTRACT

BACKGROUND AND OBJECTIVES: The purpose of this study was to provide an effective RHD genotyping strategy for the East Asian blood donors. MATERIAL AND METHODS: RhD phenotyping, weak D testing and RhCE phenotyping were performed on 110 samples from members of the RhD-negative club, private organization composed of RhD-negative blood donors, in the GwangJu-Chonnam region of Korea. The RHD promoter, intron 4, and exons 7 and 10 were analysed by real-time PCR. Two nucleotide changes (c.1227 G>A, and c.1222 T>C) in exon 9 were analysed by sequencing. RESULTS: Of 110 RhD-negative club members, 79 (71·8%) showed complete deletion of the RHD gene, 10 (9·1%) showed results consistent with RHD-CE-D hybrid, and 21 (19·1%) showed amplification of RHD promoter, intron 4, and exons 7 and 10. Of the latter group, 16 (14·5%) were in the DEL blood group including c.1227 G>A (N = 14) and c.1222 T>C (N = 2), 2 (1·8%) were weak D, 1(0·9%) was partial D, and 2 (1·8%) were undetermined. The RhD-negative phenotype samples consisted of 58 C-E-c+e+, 19 C-E+c+e+, 3 C-E+c+e-, 21 C+E-c+e-, 6 C+E-c+e+ and 3 C+E-c-e + . Notably, all 58 samples with the C-E-c+e+ phenotype were revealed to have complete deletion of the RHD gene. The C-E-c+e+ phenotype showed 100% positive predictive value for detecting D-negative cases. CONCLUSIONS: RHD genotyping is not required in half of D-negative cases. We suggest here an effective RHD genotyping strategy for accurate detection of RhD variants in apparently RhD-negative blood donors in East Asia.


Subject(s)
Blood Donors , Rh-Hr Blood-Group System/genetics , Asian People/genetics , Gene Frequency , Genotype , Humans , Polymorphism, Genetic , Real-Time Polymerase Chain Reaction , Republic of Korea , Sensitivity and Specificity , Sequence Analysis, DNA , Sequence Deletion
12.
Vox Sang ; 111(4): 441-444, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27538125

ABSTRACT

A novel A subgroup allele (c.538C>T p.Arg180Cys) showing weak A phenotype was found in a 30-year-old Korean woman with ABO discrepancy. Using 3D structural analysis, protein stability prediction and flow cytometric analysis of ABO antigen expression on HeLa cells transfected with plasmids containing the p.Arg180Cys mutant, we found that the Arg180 residue in the loop region of the A glycosyltransferases (GTA) structure plays significant role in stabilizing its closed conformation, which is required for substrate binding and catalysis study.


Subject(s)
N-Acetylgalactosaminyltransferases/genetics , ABO Blood-Group System/genetics , Adult , Enzyme Stability , Female , Genetic Association Studies , HeLa Cells , Humans , Mutation, Missense , Phenotype , Sequence Analysis, DNA
13.
Psychol Med ; 45(14): 3009-17, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26017091

ABSTRACT

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene-environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD. METHOD: In 102 children with ADHD (age 6-15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated. RESULTS: A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temporal regions. CONCLUSIONS: Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.


Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Brain/pathology , DNA Methylation , Hyperkinesis/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Adolescent , Child , Female , Gene-Environment Interaction , Genotype , Humans , Magnetic Resonance Imaging , Male , Promoter Regions, Genetic , Psychiatric Status Rating Scales , Republic of Korea
14.
Transfus Med ; 25(5): 333-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26197879

ABSTRACT

BACKGROUND: Cis-AB, a rare ABO variant, is the result of a mutated ABO gene that produces a glycosyltransferase enzyme with dual A and B glycosyltransferase activity. It may lead to ABO discrepancies and a delay in establishing the blood group. To date, there have been no reports of a de novo mutation leading to a cis-AB allele. OBJECTIVES AND METHODS: Sequencing of the ABO gene using blood and hair follicle cells from the proposita were performed along with blood from her parents. To establish maternity and paternity, short tandem repeat (STR) analysis was also performed. The A and B enzyme activities of the novel enzyme were measured in an in vitro expression study. RESULTS: A novel cis-AB allele arising from nucleotide substitution c.796A>G (p.M266V) in the B glycosyltransferase gene were discovered in the blood and hair follicle cells from the proposita, which was absent from her parents. In all 15 autosomal STR loci analysed, the probability of maternity and paternity were 0.999999 and 0.999989, respectively. The novel enzyme created 33.1% and 60.2% of A and B antigen compared to wild type A and B glycosyltransferases. CONCLUSION: A novel mechanism leading to a cis-AB allele was discovered.


Subject(s)
ABO Blood-Group System/genetics , Glycosyltransferases/genetics , Mutation , Adult , Alleles , Female , Humans
16.
Diabet Med ; 31(2): 185-91, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24147832

ABSTRACT

AIMS: Although severe hyperbilirubinaemia causes kernicterus in neonates, normal to modestly elevated bilirubin concentrations have been reported to be neuroprotective. However, the relationship between serum bilirubin concentrations and cardiovascular autonomic neuropathy in patients with Type 2 diabetes is currently unknown. This study assessed the relationships between physiological serum total bilirubin concentrations and cardiovascular autonomic neuropathy in patients with Type 2 diabetes. METHODS: A total of 2991 patients with Type 2 diabetes were investigated in this cross-sectional study. Cardiovascular autonomic neuropathy was diagnosed by a cardiovascular reflex test. According to the American Diabetes Association criteria, the degree of cardiovascular autonomic dysfunction was graded into normal, early, definite and severe. Cardiovascular autonomic neuropathy was either definite or severe in the present study. An analysis of covariance after adjustment for other covariates was performed. A logistic regression model was used to assess an association of cardiovascular autonomic neuropathy with serum total bilirubin tertiles. RESULTS: Serum total bilirubin concentrations were significantly lower in subjects with cardiovascular autonomic neuropathy. The mean total bilirubin values differed significantly according to the severity of cardiovascular autonomic dysfunction (normal 13.0 µmol/l; early 12.3 µmol/l; definite 11.8 µmol/l; severe 10.1 µmol/l; P for trend < 0.001) after adjustment for other covariates. In multivariate analysis, serum total bilirubin levels were significantly associated with cardiovascular autonomic neuropathy (odds ratio 0.36; 95% CI 0.21-0.63 for the highest vs. the lowest bilirubin tertile, P < 0.001). CONCLUSIONS: Serum total bilirubin concentrations within the physiologic range are inversely associated with the prevalence of cardiovascular autonomic neuropathy in patients with Type 2 diabetes.


Subject(s)
Bilirubin/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetic Neuropathies/blood , Diabetic Neuropathies/epidemiology , Adult , Aged , Autonomic Nervous System Diseases/blood , Autonomic Nervous System Diseases/epidemiology , Autonomic Nervous System Diseases/etiology , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/etiology , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors
17.
Diabet Med ; 31(11): 1316-22, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24910105

ABSTRACT

AIMS: To investigate the relationship between physiological serum total bilirubin concentrations and serum C-peptide levels in Korean patients with Type 2 diabetes. METHODS: A total of 588 patients with Type 2 diabetes were investigated in this cross-sectional study. Fasting C-peptide level, 2-h postprandial C-peptide level and ΔC-peptide (postprandial C-peptide minus fasting C-peptide) level were measured in all patients. RESULTS: Fasting C-peptide level, postprandial C-peptide level and ΔC-peptide level tended to be higher in patients with higher bilirubin concentrations. Partial correlation analysis showed that serum bilirubin levels were significantly correlated with fasting C-peptide level (r = 0.159, P < 0.001), postprandial C-peptide level (r = 0.209, P < 0.001) and ΔC-peptide level (r = 0.186, P < 0.001) after adjustment for other covariates. In the multivariate model, the association between serum bilirubin concentrations and serum C-peptide levels remained significant after adjustment for confounding factors including age, gender, familial diabetes, hypertension, hyperlipidaemia, BMI, HbA1c , duration of diabetes and associated liver function tests (fasting C-peptide level: ß = 0.083, P = 0.041; postprandial C-peptide level: ß = 0.106, P = 0.005; ΔC-peptide level: ß = 0.096, P = 0.015, respectively). CONCLUSIONS: Serum bilirubin concentrations within the physiological range were positively associated with serum C-peptide levels in patients with Type 2 diabetes.


Subject(s)
Bilirubin/blood , C-Peptide/blood , Diabetes Mellitus, Type 2/blood , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Oxidative Stress , Adult , Aged , Biomarkers/blood , Cross-Sectional Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Disease Progression , Fasting , Female , Hospitals, University , Humans , Hypoglycemic Agents/therapeutic use , Insulin Secretion , Insulin-Secreting Cells/drug effects , Linear Models , Male , Middle Aged , Outpatient Clinics, Hospital , Oxidative Stress/drug effects , Postprandial Period , Republic of Korea
18.
Br J Cancer ; 108(9): 1862-9, 2013 May 14.
Article in English | MEDLINE | ID: mdl-23579219

ABSTRACT

BACKGROUND: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. METHODS: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway. RESULTS: For cetuximab regimens, patients homozygous for the wild-type alleles (GG) of LIFR rs3729740 exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (GA and AA; P=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (TT) of ANXA11 rs1049550 exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (CC and CT; P=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type LIFR rs3729740 patients either with wild-type KRAS or skin toxicity (P=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type LIFR rs3729740 (P=0.044) and in those expressing minor-type ANXA11 rs1049550 (P=0.007), respectively. CONCLUSION: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.


Subject(s)
Annexins/genetics , Colorectal Neoplasms/drug therapy , Leukemia Inhibitory Factor Receptor alpha Subunit/genetics , Molecular Targeted Therapy , Neoplasm Metastasis/drug therapy , Adult , Aged , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab , Biomarkers, Tumor/genetics , Cetuximab , Colorectal Neoplasms/genetics , Disease-Free Survival , Extracellular Signal-Regulated MAP Kinases/biosynthesis , Extracellular Signal-Regulated MAP Kinases/genetics , Female , Genotype , Humans , Male , Matrix Metalloproteinase 9/biosynthesis , Matrix Metalloproteinase 9/genetics , Middle Aged , Neoplasm Metastasis/genetics , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , ras Proteins/genetics
19.
Hum Reprod ; 28(6): 1725-30, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23589535

ABSTRACT

STUDY QUESTION: How do genetics professionals assess the potential benefits and challenges of expanded carrier screening (ECS) in reproductive healthcare? SUMMARY ANSWER: Genetics professionals believe that current ECS products have major limitations and are not ready for routine use in reproductive healthcare. WHAT IS KNOWN ALREADY: Non-targeted approaches to carrier screening have been met with uneven enthusiasm from relevant professional organizations. With declining genotyping costs, it is reasonable to expect that the number of genetic conditions evaluated by carrier-screening products will continue to increase. Reproductive healthcare providers will play a critical role in the adoption of ECS and need to be prepared for the potential challenges that lie ahead. STUDY DESIGN, SIZE, DURATION: Focus groups were convened at six academic medical centers in the USA in March 2011 to examine genetics professionals' views on ECS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty genetic professionals participated in six focus groups for this study. A clinical case report was presented to each focus group to examine participants' opinions about the use of highly multiplexed forms of carrier screening in reproductive healthcare. Focus group transcripts were analyzed for major themes and thematic density across sites using qualitative data analysis software (ATLAS.ti v5.8). MAIN RESULTS AND THE ROLE OF CHANCE: Participants believed that current ECS products have major limitations pertaining to the analysis of select alleles and genetic mutations. Participants highlighted multiple interpretive and counseling challenges that reproductive healthcare providers may face in communicating ECS results to patients. Participants stressed the importance of communicating these and other limitations to patients before recommending ECS. Participants recommended collaboration with genetic counselors and medical geneticists in providing ECS. LIMITATIONS, REASONS FOR CAUTION: To the extent that ECS products have not been widely used to date, participants may have had limited familiarity and direct clinical experience with these products. Given that this study was conducted with genetic professionals from academic medical centers in the USA, participant perspectives may not be representative of professional practices and norms in other healthcare settings. WIDER IMPLICATIONS OF THE FINDINGS: In considering the use of ECS products in their practices, reproductive healthcare providers may find it helpful to consider the perspectives of genetics professionals. These specialists have considerable experience with diverse forms of genetic testing and can provide valuable insights regarding new genomic risk assessment tools such as ECS.


Subject(s)
Genetic Carrier Screening , Genetic Counseling , Health Personnel/psychology , DNA Mutational Analysis/methods , Focus Groups , Humans
20.
Phys Rev Lett ; 111(24): 243004, 2013 Dec 13.
Article in English | MEDLINE | ID: mdl-24483653

ABSTRACT

We demonstrate that the differential ac-Stark shift of a Zeeman-sensitive ground hyperfine transition in an optical trap can be eliminated by using properly polarized trapping light. We use the vector polarizability of an alkali-metal atom to produce a polarization-dependent ac-Stark shift that resembles a Zeeman shift. We study a transition from the |2S1/2,F=2,mF=-2> to the |2S1/2,F=1,mF=-1> state of 7Li to observe 0.59±0.02 Hz linewidth with interrogation time of 2 s and 0.82±0.06 s coherence time of a superposition state. Implications of the narrow linewidth and the long coherence time for precision spectroscopy and quantum information processing using atoms in an optical lattice are discussed.

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