ESTABLISHING POPULATION AND INDIVIDUAL BIOEQUIVALENCE CONFIDENCE INTERVALS

Average bioequivalence is used to assess pharmacokinetic properties of proposed generic drug before they are marketed. The limitations of average bioequivalence have led the U.S. Food and Drug Administration to propose the use of popUlation bioequivalence and individual bioequivalence. In this study, bootstrap confidence intervals were used to evaluate population bioequivalence and individual bioequivalence in the context of a 2 x 4 crossover experimental design. Two bioequivalence criteria were compared: the mean-squared difference criterion and a probability-based criterion. Simulations were conducted to study the properties of the bootstrap confidence intervals under each criterion in establishing population bioequivalence or individual bioequivalence. Various inter-subject, within-subject, and subject-by-formulation interaction variance components were considered

Development of the Risk Appraisal Measure: A Brief Screen to Identify Risk Areas and Guide Interventions for Dementia Caregivers

To develop and validate a brief screening measure for use in research, healthcare, and community settings to systematically assess well-being and identify needed areas of support for caregivers of patients with dementia. DESIGN : This study used data from Resources for Enhancing Alzheimer's Caregiver Health (REACH II), a multisite randomized clinical trial of a behavioral intervention designed to improve the quality of life of caregivers in multiple domains. SETTING : REACH II. PARTICIPANTS : Two hundred twelve Hispanic, 211 black, and 219 white family caregivers providing in-home care to patients with dementia. MEASUREMENT : Based on conceptual and psychometric analyses, a 16-item measure was developed that assesses six domains linked to caregiver risk and amenable to intervention: depression, burden, self-care and health behaviors, social support, safety, and patient problem behaviors. The reliability and validity of the instrument was evaluated with 642 dementia caregiver dyads from the REACH II program. RESULTS : The measure was found to have acceptable internal consistency for a multidimensional scale and similar measurement properties for each of the racial and ethnic groups. Concurrent validity was also demonstrated for the measure. CONCLUSION : The REACH Risk Appraisal Measure developed in this study shows promise as an assessment tool that can be used in research, clinical, and community settings to guide, prioritize, and target needed areas of support for caregivers of patients with dementia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66234/1/j.1532-5415.2009.02260.x.pd

Directional asymmetries reveal a universal bias in adult vowel perception

published online 21 April 2017Research on cross-language vowel perception in both infants and adults has shown that for many vowel contrasts, discrimination is easier when the same pair of vowels is presented in one direction compared to the reverse direction. According to one account, these directional asymmetries reflect a universal bias favoring “focal” vowels (i.e., vowels whose adjacent formants are close in frequency, which concentrates acoustic energy into a narrower spectral region). An alternative, but not mutually exclusive, account is that such effects reflect an experience-dependent bias favoring prototypical instances of native-language vowel categories. To disentangle the effects of focalization and prototypicality, the authors first identified a certain location in phonetic space where vowels were consistently categorized as /u/ by both Canadian-English and Canadian-French listeners, but that nevertheless varied in their stimulus goodness (i.e., the best Canadian-French /u/ exemplars were more focal compared to the best Canadian-English /u/ exemplars). In subsequent AX discrimination tests, both Canadian-English and Canadian-French listeners performed better at discriminating changes from less to more focal /u/’s compared to the reverse, regardless of variation in prototypicality. These findings demonstrate a universal bias favoring vowels with greater formant convergence that operates independently of biases related to language-specific prototype categorization.This research was supported by NSERC Discovery Grant No. 105397 to L.P. and NSERC Discovery Grant No. 312395 to L.M

Healthcare professionals' perceptions of pain in infants at risk for neurological impairment

BACKGROUND: To determine whether healthcare professionals perceive the pain of infants differently due to their understanding of that infant's level of risk for neurological impairment. METHOD: Neonatal Intensive Care Units (NICU's) at two tertiary pediatric centers. Ninety-five healthcare professionals who practice in the NICU (50 nurses, 19 physicians, 17 respiratory therapists, 9 other) participated. They rated the pain (0–10 scale and 0–6 Faces Pain Scale), distress (0–10), effectiveness of cuddling to relieve pain (0–10) and time to calm without intervention (seconds) for nine video clips of neonates receiving a heel stick. Prior to each rating, they were provided with descriptions that suggested the infant had mild, moderate or severe risk for neurological impairment. Ratings were examined as a function of the level of risk described. RESULTS: Professionals' ratings of pain, distress, and time to calm did not vary significantly with level of risk, but ratings of the effectiveness of cuddling were significantly lower as risk increased [F (2,93) = 4.4, p = .02]. No differences in ratings were found due to participants' age, gender or site of study. Physicians' ratings were significantly lower than nurses' across ratings. CONCLUSION: Professionals provided with visual information regarding an infants' pain during a procedure did not display the belief that infants' level of risk for neurological impairment affected their pain experience. Professionals' estimates of the effectiveness of a nonpharmacological intervention did differ due to level of risk

Higher self-reported physical activity Is associated with lower systolic blood pressure: The Dietary Intervention Study in Childhood (DISC)

Objective: Children participating in a dietary clinical trial were studied to assess physical activity patterns in boys and girls longitudinally from late childhood through puberty; and to determine the association of level of physical activity on systolic blood pressure (SBP), low density lipoprotein (LDL) cholesterol, and body mass index (BMI). Patients and Methods: In the Dietary Intervention Study in Childhood (DISC), a randomized clinical trial of a reduced saturated fat and cholesterol diet in 8-10 year olds with elevated LDL, a questionnaire that determined time spent in five intensity levels of physical activity was completed at baseline and at 1 and 3 years. A MET score was calculated for weekly activity; hours per week were calculated for intense activities. We hypothesized that weekly self-reported physical activity would be associated with lower SBP, LDL, and BMI over three years. Longitudinal data analyses were performed for each outcome (SBP, LDL, and BMI) using generalized estimating equations with MET score per week as the independent variable adjusted for visit, gender, and Tanner stage (BMI was included in models for SBP and LDL). Results: The initial study cohort comprised 663 youths (362 male; age 9.7 years, 301 female; age 9.0 years) of whom 623 (94%) completed the 3-year visit. For every 100 MET-hours of physical activity, there was a decrease of 1.15 mmHg of SBP (p=0.0038). There was a 1.28 mg/dl decline in LDL (p=0.10) for a similar energy expenditure. For BMI, an analysis of intense physical activity showed that for every 10 hours of intense activity, there was a trend toward significance with a 0.2 kg/m2 decrease (p=0.06). Conclusion: Children with elevated cholesterol who lead a more physically active lifestyle have lower SBP and a trend toward lower LDL over a 3-year interval. Long-term participation in intense physical activity may reduce BMI as well

Height, adiposity and body fat distribution and breast density in young women

INTRODUCTION: Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. METHOD: Associations of height, adiposity and body fat distribution with percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25-29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy x-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging (MRI). Associations were evaluated using linear mixed effects models. All tests of statistical significance are 2-sided. RESULTS: Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percent fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) each was associated significantly with a 44.4% - 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. However, after adjustment for childhood BMI only the DXA measures percent fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8% - 19.6% decrease in ADBV . In mutually adjusted analysis, percent fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in A:G ratio was associated with a 18.5% decrease in ADBV. CONCLUSIONS: Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations

Situating dissemination and implementation sciences within and across the translational research spectrum

The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework\u27s major proposition is that it situates D&I sciences as targeted sub-sciences of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages

A continental analysis of ecosystem vulnerability to atmospheric nitrogen deposition

Atmospheric nitrogen (N) deposition has been shown to decrease plant species richness along regional deposition gradients in Europe and in experimental manipulations. However, the general response of species richness to N deposition across different vegetation types, soil conditions, and climates remains largely unknown even though responses may be contingent on these environmental factors. We assessed the effect of N deposition on herbaceous richness for15,136 forest, woodland, shrubland, and grassland sites across the continental United States, to address how edaphic and climatic conditions altered vulnerability to this stressor. In our dataset, with N deposition ranging from 1 to 19 kg N·ha−1·y−1, we found a unimodal relationship; richness increased at low deposition levels and decreased above 8.7 and 13.4 kg N·ha−1·y−1 in open and closed-canopy vegetation, respectively. N deposition exceeded critical loads for loss of plant species richness in 24% of 15,136 sites examined nationwide. There were negative relationships between species richness and N deposition in 36% of 44 community gradients. Vulnerability to N deposition was consistently higher in more acidic soils whereas the moderating roles of temperature and precipitation varied across scales. We demonstrate here that negative relationships between N deposition and species richness are common, albeit not universal, and that fine-scale processes can moderate vegetation responses to N deposition. Our results highlight the importance of contingent factors when estimating ecosystem vulnerability to N deposition and suggest that N deposition is affecting species richness in forested and nonforested systems across much of the continental United States

Microbiomes attached to fresh perennial ryegrass are temporally resilient and adapt to changing ecological niches

Abstract Background Gut microbiomes, such as the rumen, greatly influence host nutrition due to their feed energy-harvesting capacity. We investigated temporal ecological interactions facilitating energy harvesting at the fresh perennial ryegrass (PRG)-biofilm interface in the rumen using an in sacco approach and prokaryotic metatranscriptomic profiling. Results Network analysis identified two distinct sub-microbiomes primarily representing primary (≤ 4 h) and secondary (≥ 4 h) colonisation phases and the most transcriptionally active bacterial families (i.e Fibrobacteriaceae, Selemondaceae and Methanobacteriaceae) did not interact with either sub-microbiome, indicating non-cooperative behaviour. Conversely, Prevotellaceae had most transcriptional activity within the primary sub-microbiome (focussed on protein metabolism) and Lachnospiraceae within the secondary sub-microbiome (focussed on carbohydrate degradation). Putative keystone taxa, with low transcriptional activity, were identified within both sub-microbiomes, highlighting the important synergistic role of minor bacterial families; however, we hypothesise that they may be ‘cheating’ in order to capitalise on the energy-harvesting capacity of other microbes. In terms of chemical cues underlying transition from primary to secondary colonisation phases, we suggest that AI-2-based quorum sensing plays a role, based on LuxS gene expression data, coupled with changes in PRG chemistry. Conclusions In summary, we show that fresh PRG-attached prokaryotes are resilient and adapt quickly to changing niches. This study provides the first major insight into the complex temporal ecological interactions occurring at the plant-biofilm interface within the rumen. The study also provides valuable insights into potential plant breeding strategies for development of the utopian plant, allowing optimal sustainable production of ruminants. Video Abstrac