Facilitators and barriers to the successful implementation of pediatric antibacterial drug trials: Findings from CTTI's survey of investigators.

An urgent need exists to develop new antibacterial drugs for children. We conducted research with investigators of pediatric antibacterial drug trials to identify facilitators and barriers in the conduct of these trials. Seventy-three investigators completed an online survey assessing the importance of 15 facilitators (grouped in 5 topical categories) and the severity of 36 barriers (grouped in 6 topical categories) to implementing pediatric antibacterial drug trials. Analysis focused on the identification of key factors that facilitate the successful implementation of pediatric antibacterial drug trials and the key barriers to implementation. Almost all investigators identified two factors as very important facilitators: having site personnel for enrollment and having adequate funding. Other top factors were related to staffing. Among the barriers, factors related to parent concerns and consent were prominent, particularly obtaining parental consent when there was disagreement between parents, concerns about the number of blood draws, and concerns about the number of invasive procedures. Having overly narrow eligibility criteria was also identified as a major barrier. The survey findings suggest three areas in which to focus efforts to help facilitate ongoing drug development: (1) improving engagement with parents of children who may be eligible to enroll in a pediatric antibacterial drug trial, (2) broadening inclusion criteria to allow more participants to enroll, and (3) ensuring adequate staffing and establishing sustainable financial strategies, such as funding pediatric trial networks. The pediatric antibacterial drug trials enterprise is likely to benefit from focused efforts by all stakeholders to remove barriers and enhance facilitation

Using Global Positioning Systems (GPS) and temperature data to generate time-activity classifications for estimating personal exposure in air monitoring studies: an automated method

Background: Personal exposure studies of air pollution generally use self-reported diaries to capture individuals’ time-activity data. Enhancements in the accuracy, size, memory and battery life of personal Global Positioning Systems (GPS) units have allowed for higher resolution tracking of study participants’ locations. Improved time activity classifications combined with personal continuous air pollution sampling can improve assessments of location-related air pollution exposures for health studies. Methods: Data was collected using a GPS and personal temperature from 54 children with asthma living in Montreal, Canada, who participated in a 10-day personal air pollution exposure study. A method was developed that incorporated personal temperature data and then matched a participant’s position against available spatial data (i.e., road networks) to generate time-activity categories. The diary-based and GPS-generated time-activity categories were compared and combined with continuous personal PM2.5 data to assess the impact of exposure misclassification when using diary based methods. Results: There was good agreement between the automated method and the diary method; however, the automated method (means: outdoors = 5.1%, indoors other =9.8%) estimated less time spent in some locations compared to the diary method (outdoors = 6.7%, indoors other = 14.4%). Agreement statistics (AC1 = 0.778) suggest ‘good’ agreement between methods over all location categories. However, location categories (Outdoors and Transit) where less time is spent show greater disagreement: e.g., mean time “Indoors Other” using the time-activity diary was 14.4% compared to 9.8% using the automated method. While mean daily time “In Transit” was relatively consistent between the methods, the mean daily exposure to PM2.5 while “In Transit” was 15.9 μg/m3 using the automated method compared to 6.8 μg/m3 using the daily diary. Conclusions: Mean times spent in different locations as categorized by a GPS-based method were comparable to those from a time-activity diary, but there were differences in estimates of exposure to PM2.5 from the two methods. An automated GPS-based time-activity method will reduce participant burden, potentially providing more accurate and unbiased assessments of location. Combined with continuous air measurements, the higher resolution GPS data could present a different and more accurate picture of personal exposures to air pollution

Pediatric Climate Change Advocacy: A Call to Action for Health Care Providers

Climate change already besieges us. Using specific examples this paper highlights the impacts of climate change affecting children today, particularly those who disproportionately experience those impacts and beseeches pediatricians and other healthcare professionals in all types of practice settings to engage in climate change advocacy. Examples of organizational, educational, legislative/policy, and cooperative/community advocacy are provided. Pediatricians have been quick to recognize the threat of climate change, but broader engagement is needed from all health professions

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Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative.

Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials. Of the 136 providers surveyed, 52/136 (38%) had previously referred a pediatric patient to a trial, and only 17/136 (12%) had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation

Household determinants of biocontaminant exposures in Canadian homes

Exposure to biocontaminants, such as dust mites, animal dander, bacteria, and mold, is associated with a range of health effects. This study identified household characteristics associated with indoor biocontaminant loadings in four Canadian cities. Floor dust was collected in 290 Canadian homes in Edmonton, Halifax, Montreal, and Windsor. The dust samples were analyzed for house dust mite allergens (Der f 1 and Der p 1), cat allergen (Fel d 1), cockroach allergen (Bla g 1), beta-(1,3)-D-glucan, and endotoxin. Household information was obtained through questionnaires and home inspections. We performed univariate and multivariate analyses to identify household determinants of biocontaminant loadings and mold odor presence. We observed large regional variations for all biocontaminants, except for cockroach allergen. The ranges of the contaminants measured in loadings and concentrations were similar to that of previous Canadian studies. Household characteristics including presence of carpeting, low floor cleaning frequency, older home age, presence of pets, and indoor relative humidity above 45% were positively associated with the presence of multiple indoor biocontaminants. High floor cleaning frequency and use of dehumidifiers were negatively associated with the presence of multiple indoor biocontaminants. Mold odor was positively associated with older home age, past water damage, and visible mold growth

Quantum Probes of Spacetime Singularities

It is shown that there are static spacetimes with timelike curvature singularities which appear completely nonsingular when probed with quantum test particles. Examples include extreme dilatonic black holes and the fundamental string solution. In these spacetimes, the dynamics of quantum particles is well defined and uniquely determined.Comment: 12 pages, RevTeX, no figures, A few breif comments added and typos correcte

A New Cationic Liposome DNA Complex Enhances the Efficiency of Arterial Gene Transfer In Vivo

Overview summary GAP-DLRIE/DOPE, a new cationic liposome preparation, is an efficient liposomal vector that increases gene expression in arteries compared to naked DNA or previously described cationic DNA–liposome complexes by more than 15-fold. Although less efficient than adenoviral gene transfer, these levels of gene expression represent a significant improvement in liposome transfection in vivo and approach levels observed with clinically acceptable doses of adenoviral vectors. The improvement in gene expression, together with the relative safety associated with liposomal gene transfer, suggests that such nonviral vectors may be appropriate for human gene therapy protocols which utilize catheter-based gene delivery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63105/1/hum.1996.7.15-1803.pd

Genomic regions associated with kyphosis in swine

<p>Abstract</p> <p>Background</p> <p>A back curvature defect similar to kyphosis in humans has been observed in swine herds. The defect ranges from mild to severe curvature of the thoracic vertebrate in split carcasses and has an estimated heritability of 0.3. The objective of this study was to identify genomic regions that affect this trait.</p> <p>Results</p> <p>Single nucleotide polymorphism (SNP) associations performed with 198 SNPs and microsatellite markers in a Duroc-Landrace-Yorkshire resource population (U.S. Meat Animal Research Center, USMARC resource population) of swine provided regions of association with this trait on 15 chromosomes. Positional candidate genes, especially those involved in human skeletal development pathways, were selected for SNP identification. SNPs in 16 candidate genes were genotyped in an F2 population (n = 371) and the USMARC resource herd (n = 1,257) with kyphosis scores. SNPs in <it>KCNN2 </it>on SSC2, <it>RYR1 </it>and <it>PLOD1 </it>on SSC6 and <it>MYST4 </it>on SSC14 were significantly associated with kyphosis in the resource population of swine (<it>P </it>≤ 0.05). SNPs in <it>CER1 </it>and <it>CDH7 </it>on SSC1, <it>PSMA5 </it>on SSC4, <it>HOXC6 </it>and <it>HOXC8 </it>on SSC5, <it>ADAMTS18 </it>on SSC6 and <it>SOX9 </it>on SSC12 were significantly associated with the kyphosis trait in the F2 population of swine (<it>P </it>≤ 0.05).</p> <p>Conclusions</p> <p>These data suggest that this kyphosis trait may be affected by several loci and that these may differ by population. Carcass value could be improved by effectively removing this undesirable trait from pig populations.</p

Searching for Supernovae in HETDEX Data Release 3

We have extracted 636 spectra taken at the positions of 583 transient sources from the third data release of the Hobby-Eberly Telescope Dark Energy eXperiment (HETDEX). The transients were discovered by the Zwicky Transient Facility (ZTF) during 2018-2022. The HETDEX spectra provide a potential means to obtain classifications for a large number of objects found by photometric surveys for free. We attempt to explore and classify the spectra by utilizing several template-matching techniques. We have identified two transient sources, ZTF20aatpoos = AT 2020fiz and ZTF19abdkelq, as supernova (SN) candidates. We classify AT 2020fiz as a Type IIP SN observed ∼10 days after explosion, and we propose ZTF19abdkelq as a likely Type Ia SN caught ∼40 days after maximum light. ZTF photometry of these two sources are consistent with their classifications as SNe. Beside these two objects, we have confirmed several ZTF transients as variable active galactic nuclei based on their spectral appearance, and determined the host galaxy types of several other ZTF transients