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

Carrier velocity‐field characteristics and alloy scattering potential in Si1−xGex/Si

The alloy scattering potential is an important parameter in SiGe alloys since it not only affects the velocity‐field characteristics for carrier transport, but also allows increased optical transitions by relaxing k‐selection rules. In this letter, we report on the velocity‐field measurements for relaxed and coherently strained SiGe alloys. The alloy scattering potential is obtained from a careful fit to the data. The hole velocity at any field is found to have a bowing behavior as a function of alloy composition. This reflects a strong alloy scattering potential which is calculated to be 0.6 eV for the valence band.  Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70374/2/APPLAB-63-10-1393-1.pd

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

The chiral phase transition in charge ordered 1T-TiSe2

It was recently discovered that the low temperature, charge ordered phase of 1T-TiSe2 has a chiral character. This unexpected chirality in a system described by a scalar order parameter could be explained in a model where the emergence of relative phase shifts between three charge density wave components breaks the inversion symmetry of the lattice. Here, we present experimental evidence for the sequence of phase transitions predicted by that theory, going from disorder to non-chiral and finally to chiral charge order. Employing X-ray diffraction, specific heat, and electrical transport measurements, we find that a novel phase transition occurs ~7 K below the main charge ordering transition in TiSe2, in agreement with the predicted hierarchy of charge ordered phases.Comment: 5 pages, 3 figures; includes additional experimental and theoretical results; fixed typo

Aging is associated with an earlier arrival of reflected waves without a distal shift in reflection sites

Background-Despite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (T-INF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a "distal-shift" of reflection sites. T-INF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure-flow analysis, demonstrates the expected decline with aging. Methods and Results-We studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase-contrast MRI, respectively. We assessed RWTT using wave-separation analysis (RWTTWSA) and partially distributed tube-load (TL) modeling (RWTTTL). Consistent with previous reports, T-INF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTTWSA (general population -15.0 ms/decade, P<0.001; clinical population -9.07 ms/decade, P=0.003) and RWTTTL (general -15.8 ms/decade, P<0.001; clinical -11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. TINF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance. Conclusions-RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with aging

Estimated Muscle Loads During Squat Exercise in Microgravity Conditions

Loss of muscle mass in microgravity is one of the primary factors limiting long-term space flight. NASA researchers have developed a number of exercise devices to address this problem. The most recent is the Advanced Resistive Exercise Device (ARED), which is currently used by astronauts on the International Space Station (ISS) to emulate typical free-weight exercises in microgravity. ARED exercise on the ISS is intended to reproduce Earth-level muscle loads, but the actual muscle loads produced remain unknown as they cannot currently be measured directly. In this study we estimated muscle loads experienced during squat exercise on ARED in microgravity conditions representative of Mars, the moon, and the ISS. The estimates were generated using a subject-specific musculoskeletal computer model and ARED exercise data collected on Earth. The results provide insight into the capabilities and limitations of the ARED machine

Can Reflection from Grains Diagnose the Albedo?

By radiation transfer models with a realistic power spectra of the projected density distributions, we show that the optical properties of grains are poorly constrained by observations of reflection nebulae. The ISM is known to be hierarchically clumped from a variety of observations (molecules, H I, far-infrared). Our models assume the albedo and phase parameter of the dust, the radial optical depth of the sphere averaged over all directions, and random distributions of the dust within the sphere. The outputs are the stellar extinction, optical depth, and flux of scattered light as seen from various viewing angles. Observations provide the extinction and scattered flux from a particular direction. Hierarchical geometry has a large effect on the flux of scattered light emerging from a nebula for a particular extinction of the exciting star. There is a very large spread in both scattered fluxes and extinctions for any distribution of dust. Consequently, an observed stellar extinction and scattered flux can be fitted by a wide range of albedos. With hierarchical geometry it is not completely safe to determine even relative optical constants from multiwavelength observations of the same reflection nebula. The geometry effectively changes with wavelength as the opacity of the clumps varies. Limits on the implications of observing the same object in various wavelengths are discussed briefly. Henry (2002) uses a recipe to determine the scattered flux from a star with a given extinction. It is claimed to be independent of the geometry. It provides considerably more scattering than our models, probably leading to an underestimate of the grain albedos from the UV Diffuse Galactic Light.Comment: 27 pages, including 7 figures. Accepted by Ap

The Proton Electromagnetic Form Factor F2F_2 and Quark Orbital Angular Momentum

We analyze the proton electromagnetic form factor ratio $R(Q^{2})=QF_2(Q^{2})/F_1(Q^{2})$ as a function of momentum transfer $Q^{2}$ within perturbative QCD. We find that the prediction for $R(Q^{2})$ at large momentum transfer $Q$ depends on the exclusive quark wave functions, which are unknown. For a wide range of wave functions we find that $ QF_2/F_1 \sim\ const$ at large momentum transfer, in agreement with recent JLAB data.Comment: 8 pages, 2 figures. To appear in Proceedings of the Workshop QCD 2002, IIT Kanpur, 18-22 November (2002

Monocyte subset recruitment marker profile is inversely associated with blood apoa1 levels

Dyslipidemia promotes development of the atherosclerotic plaques that characterise cardiovascular disease. Plaque progression requires the influx of monocytes into the vessel wall, but whether dyslipidemia is associated with an increased potential of monocytes to extravasate is largely unknown. Here (using flow cytometry) we examined recruitment marker expression on monocytes from generally healthy individuals who differed in lipid profile. Comparisons were made between monocyte subsets, participants and relative to participants’ lipid levels. Monocyte subsets differed significantly in their expression of recruitment markers, with highest expression being on either the classical or non-classical subsets. However, these inter-subset differences were largely overshadowed by considerable inter-participant differences with some participants having higher levels of recruitment markers on all three monocyte subsets. Furthermore, when the expression of one recruitment marker was high, so too was that of most of the other markers, with substantial correlations evident between the markers. The inter-participant differences were explained by lipid levels. Most notably, there was a significant inverse correlation for most markers with ApoA1 levels. Our results indicate that dyslipidemia, in particular low levels of ApoA1, is associated with an increased potential of all monocyte subsets to extravasate, and to do so using a wider repertoire of recruitment markers than currently appreciated

Direct measurement of the Hall factor for holes in relaxed Si1−xGex (0<x<1)

The Hall factor for holes in relaxed p‐type Si1−xGex alloys has been determined from mobility measurements at magnetic fields up to 7 T at 290 K. Our data together with previously published values for Si and Ge suggest that r for holes in SiGe varies between 0.73 and 1.7 with a possible strong bowing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70214/2/APPLAB-64-23-3110-1.pd