Highlights • Study of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7). • Immune responses to PCVs and meningococcal C conjugate vaccine (MnCCV) assessed. • Immune ...responses to MnCCV were similar when coadministered with PCV7 or PCV13. • PCV13 elicited substantial antipneumococcal responses against all 13 serotypes. • Safety and tolerability were similar between the PCV7 and PCV13 groups.
Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) were compared with 7-valent pneumococcal conjugate vaccine (PCV7) in Chinese infants.
Healthy infants aged 2 months were ...randomized to a double-blind 3-dose infant series plus 1 toddler dose of PCV7 or PCV13 at 3, 4, 5 and 12 months or open-label PCV13 at 2, 4, 6 and 12 months. Serotype-specific immunoglobulin G (IgG) binding and functionality were measured 1 month after the infant series and after the toddler dose. Local reactions, systemic events and adverse events were assessed postvaccination.
For the 7 common serotypes, serotype-specific binding IgGs elicited by PCV13 were noninferior to PCV7 after the 3-dose infant series; functional antibodies were comparable. For the 6 additional serotypes, PCV13 recipients had significantly higher serotype-specific IgGs and functional antibodies than PCV7 recipients after the infant series. The toddler dose boosted the immune response. Local reactions and systemic events were mild in severity and similar across groups. No new safety signals were identified.
For the 7 common serotypes, serotype-specific binding IgG after 2 different 3-dose regimens of PCV13 were noninferior to PCV7 responses. PCV13 recipients had significantly higher immune responses to the 6 additional serotypes. PCV13 is expected to provide pneumococcal disease protection comparable to PCV7 for the common serotypes and further protection against disease caused by the 6 additional serotypes. Safety of PCV7 and PCV13 was comparable.
Two novel coordination polymers with formulas CoL1·3H2O 1, L1 = 3,3′-((1,7-dioxa-4,10-diazacyclododecane-4,10-diyl)bis(methylene) dibenzenecarboxylate and Co2 L2(H2O)2·2(H2O) 2, L2 = ...5,5′-((1,7-dioxa-4,10-diazacyclododecane-4,10-diyl)bis(methylene)) diisophthalate were synthesized, where one Co(II) ion coordinates the crown-4 moiety of the ligand. Compound 1 crystallizes in the space group C2 as an infinite two-dimensional chiral layered coordination network with a tetragonal 44 sql net topology. The structural unit consists of the coordinated Co(II) ion and the deprotonated ligand. The Co(II) ion is 6-coordinate with two nitrogen atoms and two oxygen atoms of the crown 1,7-diaza-12-crown-4, and two carboxylate oxygen atoms from neighboring ligands, and exhibits a highly distorted octahedral geometry. Compound 2 crystallizes in the monoclinic space group P21/n as a triply interpenetrating 3D network with the uncommon sqc528/dmd system, the first coordination polymer with a 3-fold interpenetrating dmd topology. It exhibits two distinct Co(II) ions. One is in the center of the crown-4 along with two cis-coordinated water molecules in a highly distorted octahedral geometry; the other is 4-coordinate with tetrahedral geometry and a node in the framework. Weak antiferromagnetic interactions exist between the cobalt centers in both compounds.
Fine suspended sediment concentrations were measured for the periods August 1982 to July 1983; September 1992 to August 1993; August 1997 to July 1998; August 1998 to July 1999; and May 2002 to April ...2003 from eight stations in the Changjiang River estuary and adjacent coastal waters, China. Analyses of those data suggest that (1) yearly-averaged suspended sediment concentrations increased from landward to seaward, i.e. 0.13
kg
m
−3 at Xuliujing, 0.36
kg
m
−3 at Sheshan, and 1.56
kg
m
−3 at Tanhu; (2) the suspended sediment concentrations in the inner part of the estuary were higher in summer than in winter, while in the outer part of the estuary they were higher in winter than in summer; (3) the amplitude of suspended sediment concentration variations was greater in the outer part of the estuary than in the inner part of the estuary, and greater in Hangzhou Bay than in the Changjiang River estuary; (4) the fine suspended sediment concentrations had pronounced seasonal and spring-neap tidal variations; and (5) wind waves controlled seasonal variations and tidal currents controlled spring-neap tidal variations.
Silicon carbide bipolar transistor (SiC BJT) is thirdgeneration semiconductor devices, but due to the high driving loss (Edri), SiC BJT has not been widely studied and commercialized. To solve this ...problem, a Si-SiC hybrid Darlington transistor pair (HDTP) is proposed, which is composed of an input Si BJT and an output SiC BJT connected by a common emitter. Moreover, the switch loss (ESW) of the SiSiC HDTP is low because the output BJT operates in the active region. The static and dynamic characteristics of Si-SiC HDTP are analyzed through TCAD simulations and experiments. The simulation results show that carriers of output SiC BJT can be quickly accumulated and swept out during switching transient. The experiment results show that the driving losses of the Si-SiC HDTP is reduced by 95% and 63% compared with SiC BJT and traditional SiC-SiC DTP, respectively. Under VCE of 400 V and ICE of 15 A, the ESW of Si-SiC HDTP is decreased by 28.5% and 13.6% compared with SiC BJT and SiC MOSFET, respectively. During switch stress test, the Si-SiC HDTP show higher switch reliability compared to the SiC MOSFET.
Abstract Two randomized trials of 13-valent pneumococcal conjugate vaccine (PCV13) relative to PCV7 evaluated the immune responses of coadministered antigens comprising Infanrix® hexa/Infanrix® -IPV ...+ Hib (diphtheria, tetanus, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b). After the 3-dose infant series, immunogenic noninferiority was demonstrated for all concomitantly administered antigens between the PCV13 and PCV7 groups. All antigens elicited good booster responses after the toddler dose except pertussis toxoid; however, 99.6% subjects achieved pertussis toxoid protective antibody level ≥5 EU/mL in both groups. These results support the concomitant administration of PCV13 and Infanrix hexa/Infanrix-IPV + Hib as part of routine immunization schedules.
Kv1.3 channels play an important role in modulating lymphocyte proliferation and apoptosis. We hypothesized that Kv1.3 channels in B lymphocytes might be regulated by rituximab, an antibody to CD20, ...a drug for treatments of B-cell lymphomas and autoimmune diseases. Using both whole-cell and cell-attached patch-clamp techniques, we found that rituximab inhibited Kv1.3 channels in Daudi human B lymphoma cells by promoting the channel inactivation at a concentration which was much greater than that required for activation of CD20. The effect of rituximab on Kv1.3 channels was abolished after selective blockade of FcγRIIB receptors with anti-FcγRIIB antibody. Western blot experiments showed that Daudi B cells expressed both Kv1.3 channel and the low affinity Fc receptor, FcγRIIB, which could be activated by the Fc region of rituximab. In contrast, normal lymphocytes expressed less Kv1.3 channels with faster inactivation. Confocal microscopy and flow cytometry data showed that rituximab induced apoptosis of Daudi B cells and that the effect was attenuated by blockade of FcγRIIB receptors and partially mimicked by inhibition of Kv1.3 channels. These results suggest that in addition to previously described complement-dependent cytotoxicity, rituximab also induces apoptosis of malignant B lymphocyte by stimulating FcγRIIB receptors and inhibiting Kv1.3 channels.
► Both FcγRIIB receptor and Kv1.3 channel are expressed in malignant Daudi B cells. ► Compared to normal lymphocytes, Kv1.3 channel is highly expressed in Daudi cells. ► Kv1.3 channel in Daudi cells does not inactivate completely as normal lymphocytes. ► Rituximab inhibits Kv1.3 channel by promoting its inactivation via FcγRIIB receptor. ► Rituximab reduces membrane potential and induces apoptosis via FcγRIIB receptor.
Background Adaptive dose-ranging trials are more efficient than traditional approaches and may be designed to explicitly address the goals and decisions inherent in learn-phase drug development. We ...report the design, implementation, and outcome of an innovative Bayesian, response-adaptive, dose-ranging trial of an investigational drug in patients with diabetes, incorporating a dose expansion approach to flexibly address both efficacy and safety.
Purpose The design was developed to assess whether one or more doses of an investigational drug demonstrated superior efficacy to an active control while maintaining an acceptable safety profile.
Methods The trial used a two-stage design, in which patients were initially allocated equally to placebo, investigational drug at a low and a medium dose, and an active control. Movement to the second stage was contingent upon evidence of efficacy (measured by change in fasting blood glucose) to add a very low dose of the investigational drug and of safety (measured by weight gain) to add a high dose of the investigational drug. The design incorporated a longitudinal model to maximize use of incomplete data, predictive probabilities to guide the decisions to terminate the trial for futility or move on to Stage 2, and a dose-response model in Stage 2 to borrow information across adjacent doses. Extensive simulations were used to fine tune trial parameters, to define operating characteristics, and to determine the required sample sizes. A data monitoring committee was provided with frequent reports to aid in trial oversight.
Results In Stage 1, as trial data accrued, the predictive probability that either the low or medium dose of the investigational drug was superior to the active control fell to low values. Stage 1 termination was recommended after 199 subjects were randomized, out of a maximum trial size of 500 subjects, and the final sample size was 218. Thus the trial did not progress to Stage 2.
Limitations Because of the relatively narrow dose range to be assessed, and the inability to utilize the highest dose at the beginning of the trial, a fully responsive-adaptive design incorporating dose-response modeling was not considered a viable option. This limited the efficiency gains possible with a full set of adaptive design elements.
Conclusions The two-stage dose-expansion design functioned as designed, recommending early termination based on a low probability that the tested doses had efficacy greater than the active control. Clinical Trials 2010; 7: 121—135. http://ctj.sagepub.com
Objective:
Pneumococcal disease is a global problem, including in China. The objective of this study was to provide safety data for single-dose 13-valent pneumococcal conjugate vaccine (PCV13) in ...Chinese subjects, needed to begin a phase III safety and immunogenicity study in Chinese infants.
Methods:
Healthy Chinese adults (18−55 years), children (3−5 years), and infants (42–98 days) received a single dose of PCV13 in this open-label safety study. Local reactions and systemic events were collected for 7 days via an electronic diary; adverse events were recorded for 1 month after vaccination.
Results:
All 72 (24 per group) screened subjects (58.3% males; mean ± standard deviation SD age: 43.3 ± 9.1 years adults, 4.5 ± 0.7 years children, and 79.6 ± 15.2 days infants) were enrolled, received vaccine, and completed the study. The most frequently reported local reactions per group were pain at the injection site (n = 23 adults 95.8%), tenderness (n = 18 children 75%), and swelling (n = 6 infants 25%), none of which were severe. The mean duration of each local reaction was ⩽2.0 days in infants and ⩽2.4 days in children but in adults was 3.3 days for pain at the injection site and 9 days each for redness and swelling. Systemic events in adults were muscle pain (n = 5), fatigue (n = 3), and headache and joint pain (n = 1 each). One child and seven infants had disturbed sleep (increased or decreased). One adult and one child had mild fever (37.7–38.5°C, as per China Food and Drug Administration guidelines). No subject used antipyretic medication. One adverse event (bronchopneumonia in an infant) was reported, which was serious, severe, and unrelated to vaccination. There were no deaths.
Conclusions:
A single dose of PCV13 was safe and well tolerated in healthy Chinese adults, children, and infants. This study provided the safety data to enable a phase III safety and immunogenicity registration trial in Chinese infants to proceed.
P.45: The Study of LCD Module Assembly Mura Liang, John Z.; Schweiger, Robert S.; Proulx, Tina M. ...
SID International Symposium Digest of technical papers,
06/2013, Letnik:
44, Številka:
1
Journal Article
Recenzirano
The direct mechanical touching usually generates mura on a LCD panel. The touch mura cannot always be flashed in a very short period. Touch mura exists in almost every mode of LCD. In this paper, a ...new type of mura which generated during the LCD module assembly process is investigated. The research results show that LC orientation change from original alignment direction is the main driving‐force of light leakage. A solution to prevent this type of mura is proposed for industrial manufacturing process.
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