Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillintazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of\u3e50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73m2, respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of\u3e90% at MICs of/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of\u3e90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of\u3e80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children

Social Entrepreneurship and Broader Theories: Shedding New Light on the “Bigger Picture”

This article documents the results of a research workshop bringing together six perspectives on social entrepreneurship. The idea was to challenge existing concepts of the economy, the firm, and entrepreneurship in order to shed new light on social entrepreneurship and on our existing theoretical frameworks. The first two contributions use a macro-perspective and discuss the notion of adaptive societies and the tragedies of disharmonization, respectively. Taking a management perspective, the next two focus on the limits of conventional assumptions in management theory, particularly human capital theory and resource-based view. The final two contributions follow an entrepreneurship perspective highlighting the usefulness of mobilization theory and the business model lens to social entrepreneurship. Despite this diversity, all contributions share the fact that they challenge narrow definitions of the unit of analysis in social entrepreneurship; they illustrate the aspect of social embeddedness, and they argue for an open-but-disciplined diversity of theories in social entrepreneurship research

Position-sensitive detection of ultracold neutrons with an imaging camera and its implications to spectroscopy

Position-sensitive detection of ultracold neutrons (UCNs) is demonstrated using an imaging charge-coupled device (CCD) camera. A spatial resolution less than 15 $\mu$m has been achieved, which is equivalent to an UCN energy resolution below 2 pico-electron-volts through the relation $\delta E = m_0g \delta x$. Here, the symbols $\delta E$, $\delta x$, $m_0$ and $g$ are the energy resolution, the spatial resolution, the neutron rest mass and the gravitational acceleration, respectively. A multilayer surface convertor described previously is used to capture UCNs and then emits visible light for CCD imaging. Particle identification and noise rejection are discussed through the use of light intensity profile analysis. This method allows different types of UCN spectroscopy and other applications.Comment: 12 figures, 28 pages, accepted for publication in NIM

Franchising as a Strategy for Combining Small and Large Group Advantages (Logics) in Social Entrepreneurship:A Hayekian Perspective

This article develops a Hayekian perspective on social franchising that distinguishes between the end-connected logic of the small group and the rule-connected logic of the big group. Our key claim is that mission-driven social entrepreneurs often draw on the small-group logic when starting their social ventures and then face difficulties when the process of scaling shifts their operations toward a big-group logic. In this situation, social franchising offers a strategy to replicate the small group despite systemwide scaling, to mobilize decentrally accessible social capital, and to reduce agency costs through mechanisms of self-selection and self-monitoring. By employing a Hayekian perspective, we are thus able to offer an explanation as to why social franchising is a suitable scaling strategy for some social entrepreneurship organizations and not for others. We illustrate our work using the Ashoka Fellow Wellcome

Status of the UCNτ experiment

The neutron is the simplest nuclear system that can be used to probe the structure of the weak interaction and search for physics beyond the standard model. Measurements of neutron lifetime and β-decay correlation coefficients with precisions of 0.02% and 0.1%, respectively, would allow for stringent constraints on new physics. The UCNτ experiment uses an asymmetric magneto-gravitational UCN trap with in situ counting of surviving neutrons to measure the neutron lifetime, τ_n = 877.7s (0.7s)_(stat) (+0.4/−0.2s)_(sys). We discuss the recent result from UCNτ, the status of ongoing data collection and analysis, and the path toward a 0.25 s measurement of the neutron lifetime with UCNτ

Demonstrable Evidence of Beneficial Physical Outcomes from University Physical Education Activity Courses

Introduction: Engagement in physical activity (PA) is often dramatically reduced during the transition from high school into college. There appears to be more stability in PA patterns during the transition from college into post-graduate life. Consequently, researchers have highlighted the years in higher education as pivotal for shaping lasting PA habits. Sadly, there is a widespread lack of evidence regarding the outcomes from physical education activity courses (PEAC) offered on campuses of higher education. Thus, their overall value lacks validation. The purpose of this work was to offer evidence of outcomes from engagement in a single, semester-long university PEAC class. Methods: Students were recruited from a variety of classes. There were no directions provided to the instructors of the courses. For grouping, classes were categorized as aerobic- (aerobics, jogging, and walking) or sport-activity (badminton, pickle ball, self-defense, strength training, and ultimate frisbee). Students in the aerobic-activity arm were randomized to aerobic testing where they underwent a submaximal treadmill protocol and grip strength (GS) testing or body composition testing (air displacement plethysmography) and GS. Those in the sport-activity arm underwent vertical jump and GS testing. Students reported to the human performance lab in the first two and final two weeks of the semester. Paired t-tests were conducted to identify differences in pre-post outcomes. Values were carried forward, not dropped, when a subject failed to return at post-test. Results: A total of 46 students (age = 21.7 ± 4.1) were randomized into the aerobic (n=25; m/f = 11/14) or body composition arms (n=21; m/f = 7/14). Additionally, 45 students (age = 20.8 ± 3.2; m/f = 23/22) from sport-activity classes were enrolled. Participation in aerobic-activity classes resulted in improvements in estimated maximal aerobic ability (p = 0.030; 42.9 ± 9.9 vs. 44.6 ± 10.1). Participation also resulted in increases in GS for those allocated to both the aerobic (p = 0.010; 56.4 ± 21.5 vs. 60.3 ± 22.3) and body composition (p = 0.022; 54.1 ± 22.1 vs. 58.1 ± 24.6) arms. Participation did not result in changes in body composition (p = 0.817; 24.7 ± 8.5 vs. 24.6 ± 7.4) despite a near-significant increase in weight (p = 0.057; 152.7 ± 38.5 vs. 154.5 ± 37.7). Participation in sport-activity classes resulted in an improvement in vertical jump (p = 0.007; 18.2 ± 6.1 vs. 18.9 ± 6.0) and GS (p = 0.002; 65.3 ± 25.6 vs. 70.0 ± 27.8). Discussion: An important first step in rebutting challenges about the credibility and worthiness of PEAC offerings is evidencing beneficial outcomes. These results represent simple, but important, markers of change. Additional demonstrable evidence is needed to ascertain elements such as what outcomes are achievable, what classes are most effective classes, and what components from class support lasting change

Survey Responses From “Wellness for Life” Classes: Overall Value and Barriers, Motivators, and Motives Towards Physical Activity

Introduction: Skill-based sport activity classes were the historical trend, but greater numbers of higher education institutions now offer courses that encompass “wellness for life” concepts. The goal of these offerings is to guide students in the development of knowledge, skills, and behaviors to adopt and maintain healthful behaviors. There is a need to amass evidence of the outcomes arising from engagement in these classes. Purpose: The purpose of this work was to document outcomes from participation in a single, semester-long, university wellness for life class. Methods: Students were recruited from courses at two universities. Survey responses were collected in the first two and final two weeks of class. The survey items included identification of: engagement in regular physical activity (PA), perceptions about PA (“view of self as an exerciser”, “contentment with current PA level”, among others), and barriers, motivators, and motives towards PA. There were no intervention suggestions provided to instructors. Results: A total of 173 students (m/f/not identified = 51/118/4; age 19.6 ± 1.4) participated. When questioned, many students identified as being an “exerciser.” Some perceived “no need to change their program” (n=37) but most “wanted more regular exercise” (n=88). A lesser number of students identified as being a “non-exerciser.” Most all “wanted more regular exercise” (n=46), but two had “no desire to start a program.” At post-test, the respective numbers were: 37, 95, 41, and 3. Numbers did not always align due to incomplete survey responses. The perceived value of the class to current and future health, rated on a scale from 0 (no impact)-100 (most influential), improved pre-post class (p \u3c 0.001) from 61.7 (±24.5) to 67.8 (±23.5). The top barrier, motivator, and motive at pre-test were: “I need to do better at managing my time to exercise more often,” “If I better organized my time or schedule I could exercise more,” and “I get pleasure or enjoy sports so I exercise,” respectively. There was shuffling among the top choices from pre- to post-test, but the top barrier remained the same. The top motivator became, “If I had more time I would exercise more,” and the top motive became, “I feel less stress after I exercise.” Discussion: Evidenced by the pre-post responses, students feel that wellness for life classes have some benefit and that perception improves after experiencing the class. There appears to be consistency in those who view themselves as “exercisers” and “non-exercisers,” which might represent a precarious situation. There is constancy in the primary barrier to exercise – the socially acceptable answer – time. It is obvious that time management is a critical element for inclusion in these classes. Students may also benefit more if instructors would offer insight on the use of motivators and motives in overcoming personal barriers

New result for the neutron β\beta-asymmetry parameter A0A_0 from UCNA

The neutron $\beta$-decay asymmetry parameter $A_0$ defines the correlation between the spin of the neutron and the momentum of the emitted electron, which determines $\lambda=\frac{g_{A}}{g_{V}}$, the ratio of the axial-vector to vector weak coupling constants. The UCNA Experiment, located at the Ultracold Neutron facility at the Los Alamos Neutron Science Center, is the first to measure such a correlation coefficient using ultracold neutrons (UCN). Following improvements to the systematic uncertainties and increased statistics, we report the new result $A_0 = -0.12054(44)_{\mathrm{stat}}(68)_{\mathrm{syst}}$ which yields $\lambda\equiv \frac{g_{A}}{g_{V}}=-1.2783(22)$. Combination with the previous UCNA result and accounting for correlated systematic uncertainties produces $A_0=-0.12015(34)_{\mathrm{stat}}(63)_{\mathrm{syst}}$ and $\lambda\equiv \frac{g_{A}}{g_{V}}=-1.2772(20)$.Comment: 9 pages, 7 figures, updated to as-published versio