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Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12–23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients.
Methods:
Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups.
Results:
Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery.
Conclusion:
In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.
Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls.
Method
Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory Emax model we developed previously.
Results
The inhibitory Emax model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), −5.67 (dorsal raphe nucleus)].
Conclusions
This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.
Genetic alteration of cyclin-dependent kinase inhibitors has been associated with carcinogenesis mechanisms in various organs.
Objective:
This study aimed to evaluate the expression and mutational analysis of Cip/Kip family cyclin-dependent kinase inhibitors (p21CIP1/WAF1, p27KIP1 and p57KIP2) in early glottic cancer.
Methods:
Expressions of Cip/Kip family and p53 were determined by quantitative reverse transcription polymerase chain reaction and densitometry. For the analysis of p21 inactivation, sequence alteration was assessed using single-strand conformational polymorphism polymerase chain reaction. Additionally, the inactivation mechanism of p27 and p57 were investigated using DNA methylation analysis.
Results:
Reduced expression of p27 and p57 were detected in all samples, whereas the expression of p21 was incompletely down-regulated in 6 of 11 samples. Additionally, single-strand conformational polymorphism polymerase chain reaction analysis showed the p53 mutation at exon 6. Methylation of p27 and p57 was detected by DNA methylation assay.
Conclusion:
Our results suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer.
Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002–2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32–4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17–4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01–3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35–9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10–6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06–7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.
Hypermucoviscous (HV) isolates of Klebsiella pneumoniae have been linked to virulence potential in experimental infections. We examined 33 isolates of K. pneumoniae from patients with bacteraemia for the HV phenotype on agar culture, and determined their virulence potential by screening for capsular (K) serotype by polymerase chain reaction and the presence of seven virulence factor genes. Fourteen (42·4%) isolates expressed the HV phenotype and 11 of these were serotype K1 or K2; these serotypes were not identified in HV-negative isolates. The genes rmpA, rmpA2, aerobactin, wabG and allS were significantly more frequent in HV than non-HV isolates. Multilocus sequence typing identified 21 sequence types (ST), eight of which were found in HV-positive isolates and the clonal relatedness of isolates of the most frequent types (ST23 and ST11) from different hospitals was confirmed by pulsed-field gel electrophoresis. The HV phenotype was more associated with community-acquired infection with a lower frequency of fatal underlying illness, but with significantly more focal infections, notably liver abscesses. Clinicians should be aware of such clinical impacts of the HV phenotype.
The current trends in stimulated Brillouin scattering and optical phase conjugation are overviewed. This report is formed by the selected papers presented in the “Fifth International Workshop on stimulated Brillouin scattering and phase conjugation 2010” in Japan. The nonlinear properties of phase conjugation based on stimulated Brillouin scattering and photo-refraction can compensate phase distortions in the high power laser systems, and they will also open up potentially novel laser technologies, e.g., phase stabilization, beam combination, pulse compression, ultrafast pulse shaping, and arbitrary waveform generation.
The scaling of BEOL interconnect technology in ULSI circuitry requires the integration of Cu wiring with ultra-low K (ULK) dielectrics. We present the results of a study of the interaction between different-stoichiometry Ta(N)/Cu barrier processes and porous ULK dielectrics (k=2.4) at 32nm groundrules Auger and diffraction analysis of blanket wafers was used to benchmark two different stoichiometries of TaN barrier deposited using commercially-available ionized PVD sources. Comparison TEM and EDX/EELS images indicates that barrier oxidation is occurring in the low nitrogen-content Ta(N) barrier, which is absent at the higher stoichiometry. These differences are further manifested in defect-density analysis of patterned wafers comparing the two processes. These results illustrate the critical importance the TaN barrier properties play in enabling the integration of Cu/ULK interconnects at 32nm at beyond.
Our aim was to determine whether the index of left ventricular mass increases during the acute and subacute phase of Kawasaki disease, and to investigate any relationship between this index and clinical and echocardiographic variables. We performed, therefore, a retrospective study of 66 children with Kawasaki disease, having a mean age of 2.85 years, comparing the findings with those obtained from 57 normal controls, having a mean age of 2.99 years. The data from the patients used for comparison was obtained during the acute and subacute phase of the illness, as well as during the phase of convalescence. We performed correlation analysis of the findings during the acute and subacute phase, determining the relationship between the index of left ventricular mass and other variables. The index was higher (p = 0.0461), and the velocity of propagation of left ventricular early diastolic flow was lower (p < 0.0001), during the acute and subacute phase when compared to control values. The index then reduced (p = 0.0001) during the phase of convalescent when compared to the acute and subacute phase. Levels of albumin in the serum (p = 0.0193), peak E velocity (p = 0.0479), and velocity of propagation (p = 0.0360) were found to be related to the index of left ventricular mass. Significant relationships were found between the differences in this index and differences in body weight when findings during the acute and subacute phase were compared to those of the phase of convalescence. The index of left ventricular mass, therefore, is increased during the acute and subacute phase of Kawasaki disease, and is associated with altered diastolic indexes. This elevation may be due to generalized myocardial swelling from acute inflammation and increased vascular permeability. Measuring this index as a potential predictor of diastolic function should be added to studies of cardiac function during the acute and subacute phase of Kawasaki disease.
We present a technique which we have found useful for the management of congenital cholesteatoma extensively involving the middle ear.
Case report:
A five-year-old boy was presented to our department for management of a white mass on the right tympanic membrane. This congenital cholesteatoma extensively occupied the tympanic cavity. It was removed through an extended tympanotomy approach using our modified sleeve technique. The conventional tympanotomy approach was extended by gently separating the tympanic annulus from its sulcus in a circular manner. The firm attachment of the tympanic membrane at the umbo was not severed, in order to avoid lateralisation of the tympanic membrane.
Conclusion:
Although various operative techniques can be used, our modified sleeve tympanotomy approach provides a similarly sufficient and direct visualisation of the entire middle ear, with, theoretically, no possibility of lateralisation of the tympanic membrane and subsequent conductive hearing loss.
An overview on current trends in stimulated Brillouin scattering and optical phase conjugation is given. This report is based on the results of the “Second International Workshop on stimulated Brillouin scattering and phase conjugation” held in Potsdam/Germany in September 2007. The properties of stimulated Brillouin scattering are presented for the compensation of phase distortions in combination with novel laser technology like ceramics materials but also for e.g., phase stabilization, beam combination, and slow light. Photorefractive nonlinear mirrors and resonant refractive index gratings are addressed as phase conjugating mirrors in addition.
Surveillance is an important component of influenza control. This report describes the establishment and first results of the Korean Influenza Surveillance Scheme (KISS), an integrated clinical and laboratory surveillance network involving 622 public health centres (PHCs) and private clinics. Sentinel physicians reported cases of influenza-like illness (ILI) weekly and forwarded specimens for virus isolation and characterization. Influenza activity during the opening 2000–2001 season was milder and delayed compared with previous years. The ILI consultation rate corresponded well with the number of influenza virus isolates, both peaking in week 10 of 2001. Influenza A(H3N2) was the dominant isolate. The peak ILI consultation rate was higher in private clinics than in PHCs (5·04 vs 1·79 cases/1000 visits). An evaluation questionnaire generated potential enhancements to the scheme. KISS appears to represent the pattern of influenza activity accurately and will have a valuable role in monitoring and preventing epidemics in Korea.
The combination of hypoplastic left heart syndrome and a right-sided aortic arch is extremely rare and lethal. To the best of our knowledge, no patient with this combination has previously been reported as surviving initial palliation. The anatomic variant is associated with abnormalities in the arteries branching from the aortic arch, making it difficult to construct a reliable source of flow of blood to the lungs. We present here a patient with this combination who survived an initial Damus-Kay-Stansel procedure combined with placement of a conduit from the right ventricle to the pulmonary arteries, and who has subsequently undergone a successful bidirectional cavopulmonary anastomosis. We believe that the conduit placed from the right ventricle provides the most reliable source of flow of blood to the lungs at the time of initial palliation in this usual combination of cardiac lesions.
Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
Modern telecommunications require materials with high dielectric constants (κ). The number of suitable elements ultimately limits one approach to the discovery of new materials, targeting compositions with high atomic polarizabilities (α). By decreasing the molar volume of compositions with high α, however, we anticipated dramatic increases in κ and demonstrated that this approach works. The quenched high-pressure perovskite polymorph of Na2MTeO6 (M = Ti, Sn) showed a twofold increase in κ, compared to the ilmenite form. This result suggested the highest values of κ occur for compositions with high α, which form quenchable compounds at high pressures and temperatures.
InGaN/GaN multi-quantum well (MQW) laser diodes (LDs) were grown on c-plane sapphire substrates using a multi-wafer MOCVD system. The threshold current for pulsed lasing was 1.6 A for a gain-guided laser diode with a stripe of 10 × 800 μm2. The threshold current density was 20.3 kA cm−2 and the threshold voltage was 16.5 V. The optical power ratio of transverse electric mode to transverse magnetic mode was found to be greater than 50. The characteristic temperature measured from the plot of threshold current versus measurement temperature was between 130 and 150K.