Zero-order controlled release of ciprofloxacin-HCl from a reservoir-based, bioresorbable and elastomeric device

A reservoir-based device constructed of a completely biodegradable elastomer can enable several new implantation and insertion options for localized drug therapy, particularly in the case of urological therapies. We performed an in vitro performance evaluation of an implantable, bio-resorbable device that supplies short-term controlled release of ciprofloxacin-HCl (CIP). The proposed device functions through a combination of osmosis and diffusion mechanisms to release CIP for short-term therapies of a few weeks duration. Poly(glycerol-co-sebacic acid) (PGS) was cast in a tubular geometry with solid drug powder packed into its core and a micro-machined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice sizes in which controlled zero-order release was the main form of drug expulsion from the device. It is demonstrated that PGS is sufficiently permeable to water to allow the design of an elementary osmotic pump for drug delivery. Indeed, PGS's water permeability is several orders of magnitude larger than commonly used cellulose acetate for elementary osmotic pumps.Deshpande Center for Technological InnovationSamsung Scholarship Foundatio

Theoretical Risk of Genetic Reassortment Should Not Impede Development of Live, Attenuated Rift Valley Fever (RVF) Vaccines Commentary on the Draft WHO RVF Target Product Profile

In November 2019, The World Health Organization (WHO) issued a draft set of Target Product Profiles (TPPs) describing optimal and minimally acceptable targets for vaccines against Rift Valley fever (RVF), a Phlebovirus with a three segmented genome, in both humans and ruminants. The TPPs contained rigid requirements to protect against genomic reassortment of live, attenuated vaccines (LAVs) with wild-type RVF virus (RVFV), which place undue constraints on development and regulatory approval of LAVs. We review the current LAVs in use and in development, and conclude that there is no evidence that reassortment between LAVs and wild-type RVFV has occurred during field use, that such a reassortment event if it occurred would have no untoward consequence, and that the TPPs should be revised to provide a more balanced assessment of the benefits versus the theoretical risks of reassortment

Safety and immunogenicity of Rift Valley fever MP-12 and arMP-12ΔNSm21/384 vaccine candidates in goats (Capra aegagrus hircus) from Tanzania

Vaccination of domestic ruminants is considered to be an effective strategy for protecting these animals against Rift Valley fever (RVF), but available vaccines have limitations. Therefore, the aim of this study was to determine the safety and immunogenicity of RVF virus (RVFV) mutagenesis passage 12 (MP-12) and arMP-12ΔNSm21/384 vaccine candidates in goats (Capra aegagrus hircus) in Tanzania. Goats were vaccinated intramuscularly with RVFV MP-12 or arMP-12ΔNSm21/384, and then on Day 87 post-vaccination (PV) all animals were revaccinated using the RVFV MP-12 vaccine candidate. Serum samples were collected from the animals before and after vaccination at various intervals to test for RVFV using a Vero cell culture assay and reverse transcription polymerase chain reaction and for RVFV-neutralising antibody using a plaque reduction neutralisation assay. Serum samples collected before vaccination on Days -14 and 0, and on Days 3, 4 and 5 PV were negative for RVFV and neutralising antibody. All animals remained healthy, and viremia was not detected in any of the animals. Rift Valley fever virus antibody was first detected on Day 5 PV at a 1:10 dilution in five of five animals vaccinated with the MP-12 vaccine and in five of eight animals vaccinated with arMP-12ΔNSm21/384. Titres then increased and were sustained at 1:40 to 1:640 through to Day 87 PV. All animals that were revaccinated on Day 87 PV with MP-12 developed antibody titres ranging from 1:160 to as high as 1:10 240 on Days 14 and 21 PV. Although the antibody titres for goats vaccinated with RVF MP-12 were slightly higher than titres elicited by the arMP-12ΔNSm21/384 vaccine, these findings demonstrated that both vaccines are promising candidates for the prevention of RVF among Tansanian goats

Analysis of multidrug resistance in the predominant Streptococcus pneumoniae serotypes in Canada:the SAVE study, 2011-15

Objectives: This study assessed MDR invasive isolates of Streptococcus pneumoniae, in relation to serotype evolution in Canada between 2011 and 2015 as part of the annual SAVE study. Methods: As part of a collaboration between the Canadian Antimicrobial Resistance Alliance and Public Health Agency of Canada-National Microbiology Laboratory, 6207 invasive isolates of S. pneumoniae were evaluated. All isolates were serotyped and had antimicrobial susceptibility testing performed, in accordance with CLSI guidelines (M07-A10, 2015). Complete susceptibility profiles were available for 6001 isolates. MDR was defined as resistance to three or more classes of antimicrobial agents (with penicillin MIC ≥2 mg/L defined as resistant). Results: The overall rate of MDR S. pneumoniae was 6.2% (372/6001) in SAVE, decreasing significantly from 8.5% in 2011 to 5.6% in 2015 (P = 0.0041). MDR was observed in 32 serotypes, with serotypes 15A and 19A predominating (26.6% and 41.7% of the MDR isolates, respectively). The overall proportion of serotypes 19A, 7F and 33A decreased significantly (P 5%) for 24F and 33F. Conclusions: In 2015, 56.3% of invasive MDR S. pneumoniae were serotypes included in the PCV-13 vaccine. PCV-13 includes the most commonly identified serotype, 19A; however, other increasingly important MDR serotypes, such as 15A, 24F and 33F, are notably not in the currently used vaccines

Texas Business Review, May 1962

The Business Situation in Texas; The Securities Boom in Texas; Part I of A Two-Part Legal Review: Construction Liens in Texas; Building Construction at New High; Retail Sales in First QuarterBureau of Business Researc