A Phase II, Randomized Study on an Investigational DTPw-HBV/Hib-MenAC Conjugate Vaccine Administered to Infants in Northern Ghana

BACKGROUND: Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana. METHODS AND FINDINGS: In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres > or = 1:8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres > or = 1:8 or SBA-MenC titres > or = 1:8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 microg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 microg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6-28.1] of doses vs 14.1%; 95% CI [10.9-17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study. CONCLUSIONS: Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN35754083

Degree of leanness and managerial commitment in an aerospace company

Lean manufacturing is a popular concept practiced in most Japanese and western company to increase their competitiveness. However, only few of them succeed to get good result. To achieve success in implementation of lean manufacturing, company has to make changes. Managerial commitment is important in this investment. Thus, the objective of this paper is to determine the degree of leanness and managerial commitment in companies. All the information of lean manufacturing practice and role of management in the implementation were compiled from related journal, book and website. Basically, this paper refers to three published journal papers by Karlsson et al. (1996), Boyer (1996), and Soriano-Meier et al. (2002). A study was conducted in an aerospace manufacturer in Malaysia. A five-point scale questionnaire has been selected to be the study instrument. These questionnaires were distributed to 45 employees work in kitting department and 8 top management people. The results indicate that the degree of leanness and managerial commitment of the company were moderate

Programmed Cell Death in Zebrafish Rohon Beard Neurons Is Influenced by TrkC1/NT-3 Signaling

AbstractRohon Beard (RB) cells are embryonic primary sensory neurons that are removed by programmed cell death during larval development in zebrafish. RB somatosensory functions are taken over by neurons of the dorsal root ganglia (DRG), suggesting that RB cell death may be triggered by the differentiation of these ganglia, as has been proposed to be the case in Xenopus. However, here we show that the timing of RB cell death correlates with reduced expression of trkC1, the receptor for neurotrophin NT-3, but not with the appearance of DRG, which differentiate only after most RB cells die. trkC1 is expressed in subpopulations of RB neurons during development, and cell death is initiated only in trkC1-negative neurons, suggesting a role for TrkC1 and its ligand, NT-3, in RB cell survival. In support of this, antibodies that deplete NT-3 induce RB cell death while exogenous application of NT-3 reduces death. In addition, we show that RB cell death can be prevented using a caspase inhibitor, zVADfmk, showing that during normal development, RB cells die by a caspase-dependent programmed cell death pathway possibly triggered by reduced signaling via TrkC1

Laboratory evaluation of large-scale decontamination approaches

Aims: To evaluate the effectiveness of two spray-based decontamination methods for surface contamination reduction and to determine the potential for contamination spread by these methods. Methods and Results: Material coupons (treated plywood and concrete) were contaminated with c. 1 × 107 spores of Bacillus atrophaeus by aerosol deposition. Decontaminants (pH-adjusted bleach or Spor-Klenz® RTU) were applied to coupons by either backpack sprayer or gas-powered sprayer. Contact time, reapplication frequency and rinse method were also varied. In addition to surface removal efficacy, partitioning of contamination between the rinsate and aerosol fractions was determined. Results indicated that pH-adjusted bleach was effective (≥6 logs reduction) when two applications and a 30 min contact time were administered, regardless of the decontaminant application method or material. Spor-Klenz® RTU was effective on wood, but achieved ≤3 logs reduction on concrete. A shortened application procedure with pH-adjusted bleach resulted in lower efficacy on wood, and a greater apparent potential for contamination spread. Conclusions: Consideration of material surface type is important when selecting a decontaminant. Also, achieving conditions that effectively inactivate surface biological contamination are critical to preventing the spread of contamination. Significance and Impact of the Study: Results presented here are intended to help development of remediation plans following a biological contamination incident

An assessment of the computer based review program of the College of Medical Radiation Technology

The study used the descriptive survey design with a population of 160 senior interns from the College of Medical Radiation Technology - De La Salle Health Sciences Institute. Respondents were selected using stratified random sampling. A self-made questionnaire was used. Responses were subjected to statistical measures, namely: frequency, percentage, mean, standard deviation, independent t-test and analysis of variance (ANOVA). Based on the findings of the study, the following conclusions were drawn: 1) Majority of the respondents are female and with a monthly family income of Php 60,000 to Php 99,000; 2) The respondent have a good assessment of the Computer Based Review Program of the College of Medical Radiation Technology in terms of eight dimensions of e-learning (pedagogical, technological, interference design, evaluation, management, resource support, ethical and institutional). Item analysis revealed that although the assessment of the Computer Based Review Program was good, the respondents recommended that further improvement of contents should be done. This recommendation is aligned with the item “I am provided with examples of previous students’ work to help me understand the content better” ranking second to the lowest among 28 items; 3) There are no significant differences in the assessment of the Computer Based Review Program when the respondents are grouped according to gender and monthly family income

Small Molecule Targeting of Specific BAF (mSWI/SNF) Complexes for HIV Latency Reversal

The persistence of a pool of latently HIV-1-infected cells despite combination anti-retroviral therapy treatment is the major roadblock for a cure. The BAF (mammalian SWI/SNF) chromatin remodeling complex is involved in establishing and maintaining viral latency, making it an attractive drug target for HIV-1 latency reversal. Here we report a high-throughput screen for inhibitors of BAF-mediated transcription in cells and the subsequent identification of a 12-membered macrolactam. This compound binds ARID1A-specific BAF complexes, prevents nucleosomal positioning, and relieves transcriptional repression of HIV-1. Through this mechanism, these compounds are able to reverse HIV-1 latency in an in vitro T cell line, an ex vivo primary cell model of HIV-1 latency, and in patient CD4+ T cells without toxicity or T cell activation. These macrolactams represent a class of latency reversal agents with unique mechanism of action, and can be combined with other latency reversal agents to improve reservoir targeting

Safety of primary immunization with a DTwP-HBV/Hib vaccine in healthy infants: a prospective, open-label, interventional, phase IV clinical study

Objective: This study aimed to assess the safety of a fully liquid DTwP-HBV/Hib pentavalent vaccine (EupentaTM) based on the occurrence of adverse events (AEs) following vaccination. Methods: This was a prospective, open-label, single-arm, interventional phase IV study. A single intramuscular injection of the study vaccine was administered to infants at approximately 6, 10, and 14 weeks of age, and an end-of-study follow-up visit was scheduled at 18 weeks. Results: In all, 3000 subjects were enrolled and received at least one dose of the study vaccine. Of these, 2717 (90.6%) experienced at least one AE. Immediate reactions, solicited and unsolicited AEs were respectively identified in 224 (7.5%), 2,652 (88.4%), and 1,099 (36.6%) subjects. The most prevalent solicited and unsolicited AEs comprised pain/tenderness and upper respiratory tract infection, respectively. Most AEs were mildly or moderately severe. Forty-one (1.4%) subjects had at least one serious AE (SAE); of these, two (0.1%) had two SAEs each, considered related to the study vaccine. Six (0.2%) subjects died due to unsolicited AEs, none of which were considered related to the study vaccine. No AEs were reported at the end-of-study follow-up visit. Conclusions: The study vaccine had a safety profile similar to that reported in a previous clinical study, and did not result in an increased risk of AEs known to be associated with DTwP-based vaccines or previously unrecognized SAEs