Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media

Electro-Haptic Stimulation: A New Approach for Improving Cochlear-Implant Listening

Cochlear implants (CIs) have been remarkably successful at restoring speech perception for severely to profoundly deaf individuals. Despite their success, several limitations remain, particularly in CI users’ ability to understand speech in noisy environments, locate sound sources, and enjoy music. A new multimodal approach has been proposed that uses haptic stimulation to provide sound information that is poorly transmitted by the implant. This augmenting of the electrical CI signal with haptic stimulation (electro-haptic stimulation; EHS) has been shown to improve speech-in-noise performance and sound localization in CI users. There is also evidence that it could enhance music perception. We review the evidence of EHS enhancement of CI listening and discuss key areas where further research is required. These include understanding the neural basis of EHS enhancement, understanding the effectiveness of EHS across different clinical populations, and the optimization of signal-processing strategies. We also discuss the significant potential for a new generation of haptic neuroprosthetic devices to aid those who cannot access hearing-assistive technology, either because of biomedical or healthcare-access issues. While significant further research and development is required, we conclude that EHS represents a promising new approach that could, in the near future, offer a non-invasive, inexpensive means of substantially improving clinical outcomes for hearing-impaired individuals

Experience in Production of 68Ga-DOTA-NOC for Clinical Use Under an Expanded Access IND

[68Ga]Ga-DOTA-NOC was produced under an Expanded Access IND for 174 clinical PET/CT studies to evaluate patients with neuroendocrine tumors. Production employed either the TiO2-based Eckert & Ziegler (EZAG) 68Ge/68Ga-generator (with fractionated elution), or the SiO2-based ITG 68Ge/68Ga-generator. In both cases, [68Ga]Ga-DOTA-NOC was reliably produced, without pre-synthesis purification of the68Ga generator eluate, using readily-implemented manual synthesis procedures. [68Ga]Ga-DOTA-NOC radiochemical purity averaged 99.2±0.4%. Administered 68Ga dose averaged 181±22 MBq, and administered peptide mass averaged 43.2±5.2 µg (n=47) and 23.9±5.7 µg (n=127), respectively, using the EZAG and ITG generators. At dose expiration, 68Ge breakthrough in the final product averaged 2.7×10−7% and 5.4×10−5% using the EZAG and ITG generators, respectively

Using the perceptions of chemical engineering students and graduates to develop employability skills

Recent years have seen increased global industry sector demand for chemical engineers, subsequent growth of Chemical Engineering (CE) degrees, producing additional qualified graduates. The Confederation of Business Industry have regularly indicated that employers are dissatisfied with skills sets offered by graduates; a 2004 World Chemical Engineering Council (WCEC) survey of experienced and newly employed chemical engineers’ perceptions of their own work skills indicated highest importance for general transferrable skills, with technical knowledge ranked considerably lower. A decade later, we investigate whether chemical engineers, both employed and in education, have similar skills perceptions, by surveying CE undergraduates in penultimate and final years of study, and CE alumni employed in CE roles; all from the University of Strathclyde. Again, transferrable skills were perceived as most important to respondents; as undergraduates gained industrial experience, a shift in perceived relative importance of technical knowledge occurred, again similar to the WCEC survey, otherwise, alumni and students had similar opinions regarding perceived degree of learning of various skills. Alumni were more critical of the quality of education with regards to management and transferrable skills, while female participants perceived business skills as undertaught, feeling considerably overexposed to the potential of research compared to male colleagues. Focus groups showed that male undergraduates valued ‘technical knowledge’ and ‘communicating professionally’; by contrast, female graduates highlighted ‘initiative’ and ‘business skills’. Consequently, training sessions were developed, focussing on transferable skills identified as important by all groups, to be delivered during academic year inductions, aligning skills to year curricula

Performance of a 62Zn/62Cu microgenerator in kit-based synthesis and delivery of [62Cu]Cu–ETS for PET perfusion imaging

The performance of a commercially produced 62Zn/62Cu microgenerator system, and an associated kit-based radiopharmaceutical synthesis method, was evaluated for clinical site production of [62Cu]Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)), an investigational agent for PET perfusion imaging. Using 37 generators, containing 1.84 ± 0.23 GBq 62Zn at 9:00 AM on the day of clinical use, a total of 45 patient doses of [62Cu]Cu-ETS (672 ± 172 MBq) were delivered without difficulty. 62Cu elution yields were high (approximately 90%), accompanied by extremely low 62Zn breakthrough (<0.001%). Radiopharmaceutical preparation, from the start-of-elution to time-of-injection, consumed less than five minutes. The 62Zn/62Cu microgenerator was a dependable source of short-lived positron-emitting 62Cu, and the kit-based synthesis proved to be rapid, robust, and highly reliable for “on-demand” delivery of [62Cu]Cu-ETS for PET perfusion imaging

Dietary Supplementation with Ethyl Ester Concentrates of Fish Oil (n-3) and Borage Oil (n-6) Polyunsaturated Fatty Acids Induces Epidermal Generation of Local Putative Anti-Inflammatory Metabolites

Clinical reports have attributed the amelioration of chronic inflammatory skin disorders to the presence of certain polyunsaturated fatty acids (PUFA) in dietary oils. To test the hypothesis of a local modulatory effect of these PUFA in the epidermis, the basal diet of normal guinea pigs was supplemented with ethyl esters of either fish oil [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] or borage oi1 [rich in gamma-linolenic acid (GLA)]. Our data demonstrated that dietary oils influence the distribution of PUFA in epidermal phospholipids and the epidermal levels of PUFA-derived hydroxy fatty acids. Specifically, animals supplemented with ethyl esters of fish oil markedly incorporated EPA and DHA into epidermal phospholipids, which paralleled the epidermal accumulation of 1 5-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDoHE). Similarly, animals supplemented with esters of borage oil preferentially incorporated dihomogammalinolenic acid (DGLA), the epidermal elongase product of GLA, into the epidermal phospholipids, which also was ac- companied by epidermal accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE). By factoring the epidermal levels of the 15-lipoxygenase products and their relative inhibitory potencies, we evolved a measure of the overall potential of dietary oils to exert local anti-inflammatory effect. For example, the leukotriene inhibition potentials (LIP) of both fish oil and borage oil were greatly enhanced when compared to controls. Thus, the altered profiles of epidermal 15-lipoxygenase products generated from particular dietary oils may be responsible, at least in part, for reported ameliorative effects of oils on chronic inflammatory skin disorders

The SBF Survey of Galaxy Distances. IV. SBF Magnitudes, Colors, and Distances

We report data for $I$ band Surface Brightness Fluctuation (SBF) magnitudes, V-I colors, and distance moduli for 300 galaxies. The Survey contains E, S0 and early-type spiral galaxies in the proportions of 49:42:9, and is essentially complete for E galaxies to Hubble velocities of 2000 km/s, with a substantial sampling of E galaxies out to 4000 km/s. The median error in distance modulus is 0.22 mag. We also present two new results from the Survey. (1) We compare the mean peculiar flow velocity (bulk flow) implied by our distances with predictions of typical cold dark matter transfer functions as a function of scale, and find very good agreement with cold, dark matter cosmologies if the transfer function scale parameter $\Gamma$, and the power spectrum normalization $\sigma_8$ are related by $\sigma_8 \Gamma^{-0.5} \approx 2\pm0.5$. Derived directly from velocities, this result is independent of the distribution of galaxies or models for biasing. The modest bulk flow contradicts reports of large-scale, large-amplitude flows in the $\sim200$ Mpc diameter volume surrounding our Survey volume. (2) We present a distance-independent measure of absolute galaxy luminosity, \Nbar, and show how it correlates with galaxy properties such as color and velocity dispersion, demonstrating its utility for measuring galaxy distances through large and unknown extinction.Comment: Accepted for publication in ApJ (10 January 2001); 23 page

14- by 22-Foot Subsonic Tunnel Laser Velocimeter Upgrade

A long-focal length laser velocimeter constructed in the early 1980's was upgraded using current technology to improve usability, reliability and future serviceability. The original, free-space optics were replaced with a state-of-the-art fiber-optic subsystem which allowed most of the optics, including the laser, to be remote from the harsh tunnel environment. General purpose high-speed digitizers were incorporated in a standard modular data acquisition system, along with custom signal processing software executed on a desktop computer, served as the replacement for the signal processors. The resulting system increased optical sensitivity with real-time signal/data processing that produced measurement precisions exceeding those of the original system. Monte Carlo simulations, along with laboratory and wind tunnel investigations were used to determine system characteristics and measurement precision

Estimation of Radiation Dosimetry for 68Ga-HBED-CC (PSMA-11) in Patients with Suspected Recurrence of Prostate Cancer

Introduction This study was performed to estimate the human radiation dosimetry for [68Ga]Ga-HBED-CC (PSMA-11) (68Ga PSMA-11). Methods Under an RDRC-approved research protocol, we evaluated the biodistribution and pharmacokinetics of 68Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical [11C]acetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0–10 min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Results Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68Ga PSMA-11 than using 11C-acetate. Conclusion Kidneys are the critical organ following 68Ga PSMA-11 administration, receiving an estimated dose of 0.413 mGy/MBq. Advances in knowledge and implications for patient care This study confirms that the kidneys will be the critical organ following intravenous administration of 68Ga PSMA-11, and provided data consistent with the expectation that 68Ga PSMA-11 will be superior to [11C]acetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse