Hardy-Muckenhoupt Bounds for Laplacian Eigenvalues

We present two graph quantities Psi(G,S) and Psi_2(G) which give constant factor estimates to the Dirichlet and Neumann eigenvalues, lambda(G,S) and lambda_2(G), respectively. Our techniques make use of a discrete Hardy-type inequality due to Muckenhoupt

\u3cem\u3eRhizobium japonicum\u3c/em\u3e Mutants Defective in Symbiotic Nitrogen Fixation

Rhizobium japonicum strains 3I1b110 and 61A76 were mutagenized to obtain 25 independently derived mutants that produced soybean nodules defective in nitrogen fixation, as assayed by acetylene reduction. The proteins of both the bacterial and the plant portions of the nodules were analyzed by two-dimensional polyacrylamide gel electrophoresis. All of the mutants had lower-than-normal levels of the nitrogenase components, and all but four contained a prominent bacteroid protein not observed in wild-type bacteroids. Experiments with bacteria grown ex planta suggested that this protein was derepressed by the absence of ammonia. Nitrogenase component II of one mutant was altered in isoelectric point. The soluble plant fraction of the nodules of seven mutants had very low levels of heme, yet the nodules of five of these seven mutants contained the polypeptide of leghemoglobin. Thus, the synthesis of the globin may not be coupled to the content of available heme in soybean nodules. The nodules of the other two of these seven mutants lacked not only leghemoglobin but most of the other normal plant and bacteroid proteins. Ultrastructural examination of nodules formed by these two mutants indicated normal ramification of infection threads but suggested a problem in subsequent survival of the bacteria and their release from the infection threads

Advancing Pediatric Antibacterial Drug Development: A Critical Need to Reinvent our Approach.

The Clinical Trials Transformation Initiative convened with several groups in the pediatric antibacterial drug development community with the goal of identifying challenges and recommending ways to improve current practice. Attention to 5 major areas hold the promise of making new antibiotics available for use in children as soon as possible after they are approved for use in adults

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

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

Affective and perceptual responses during reduced-exertion high-intensity interval training (REHIT)

We have previously demonstrated that reduced-exertion high-intensity interval training (REHIT) is a genuinely time-efficient exercise strategy for improving cardiometabolic health. Here, we examined the affective and perceptual responses to REHIT. Eight young men and women (age 21 ± 1 y, BMI 24.9 ± 2.1 m/kg2, V̇O2max 39 ± 10 ml/kg/min) and 11 men with type 2 diabetes (T2D; age 52 ± 6 y, BMI 29.7 ± 3.1 m/kg2, V̇O2max 29 ± 5 ml/kg/min) took part in three-arm crossover trials with RPE and affective valence measured during, and enjoyment and exercise preferences measured following either: 1) REHIT (2 × 20-s sprints in a 10-min exercise session), 2) HIIT (10 × 1-min efforts) and 3) 30 min MICT. Furthermore, 19 young men and women (age 25 ± 6 y, BMI 24 ± 4 m/kg2, V̇O2max 34 ± 8 ml/kg/min) completed a 6-week REHIT intervention with affective valence during an acute REHIT session measured before and after training. Affect decreases (briefly) during REHIT, but recovers rapidly, and the decline is not significantly different when compared to MICT or HIIT in either healthy participants or T2D patients. Young sedentary participants reported similar levels of enjoyment for REHIT, MICT and HIIT, but 7 out of 8 had a preference for REHIT. Conversely, T2D patients tended to report lower levels of enjoyment with REHIT compared with MICT. The decrease in affective valence observed during an acute REHIT session was significantly attenuated following training. We conclude that affective and perceptual responses to REHIT are no more negative compared to those associated with MICT or HIIT, refuting claims that supramaximal sprint interval training protocols are associated with inherent negative responses

Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.

The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings