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This article deals with the manner in which Andersen Consulting trains its HR consultants. In the face of the new complexity of HR, where new executive buyers are demanding HR solutions with business value, new ways must be found to bring professionals to high performance levels. Consultants must be armed with a broader and deeper set of competenciesnot just in HR skills but in general business and interpersonal skills, and in technology. The article addresses new kinds of delivery philosophies and mechanisms-finding the right delivery for the right kind of training. It then presents an overview of the general curriculum for Andersen's consulting professionals and the specialized curriculum for those concentrating on HR delivery. (c) 1999 John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

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Highly selective C-H functionalization remains an ongoing challenge in organic synthetic methodologies. Biocatalysts are robust tools for achieving these difficult chemical transformations. Biocatalyst engineering has often required directed evolution or structure-based rational design campaigns to improve their activities. In recent years, machine learning has been integrated into these workflows to improve the discovery of beneficial enzyme variants. In this work, we combine a structure-based machine-learning algorithm with classical molecular dynamics simulations to down select mutations for rational design of a non-heme iron-dependent lysine dioxygenase, LDO. This approach consistently resulted in functional LDO mutants and circumvents the need for extensive study of mutational activity before-hand. Our rationally designed single mutants purified with up to 2-fold higher yields than WT and displayed higher total turnover numbers (TTN). Combining five such single mutations into a pentamutant variant, LPNYI LDO, leads to a 40% improvement in the TTN (218±3) as compared to WT LDO (TTN = 160±2). Overall, this work offers a low-barrier approach for those seeking to synergize machine learning algorithms with pre-existing protein engineering strategies., (© 2024 Wiley‐VCH GmbH.)

Studies on the occurrence and environmental distribution of per- and polyfluoroalkyl substances (PFAS) have clearly demonstrated their ubiquity in surface soil as a result of historic and ongoing emissions from various manufacturing and industrial activities worldwide. Given global efforts to characterize and mitigate risk from point source-impacted sites, there is, thus, an urgent need to quantify nonpoint source threshold concentrations (i.e., background) to support site management decisions particularly for perfluorooctane sulfonate (PFOS) as a top priority. Accordingly, this study evaluated the application of Gaussian mixture models (GMMs) fitted to log-transformed PFOS concentrations using nation-wide metadata consisting of thousands of surface soil samples representative of both background and aqueous film-forming foam (AFFF) impacts with unknown proportion. Multiple GMMs were fitted for a given number of components using different methods to account for bias associated with a marginal non-detect fraction (n = 8%) including exclusion, substitution, and imputation. Careful evaluation of the rate of change among multiple goodness-of-fit measures universally justified fitting a 2-component GMM; thus, discriminating between background and AFFF-impacted samples among the metadata. Background threshold PFOS concentrations were defined as the intersection of the probability density functions and ranged between 1.9 and 13.8 µg/kg within a broader concentration range extending up to ~ 50,000 µg/kg reflecting AFFF impacts. By demonstrating an innovative statistical approach that intelligently incorporates different criteria for model selection, this research makes significant contributions to risk mitigation efforts at point source-impacted sites and lays the groundwork for future targeted regulatory actions., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To examine the relationship between changes in American Academy of Pediatrics (AAP) guidance and palivizumab use for infants admitted to the NICU. We hypothesized that each change in guidance would be associated with a change in palivizumab usage., Methods: This is a retrospective repeated cross-sectional study of palivizumab usage in defined subgroups of infants discharged between 1999 and 2020 using the Pediatrix Clinical Data Warehouse., Results: Palivizumab utilization increased in all groups between 1999 and 2003 and remained stable until 2013. Large changes in palivizumab use occurred between 2013 and 2015 followed by slower changes from 2016 to 2020. The largest decrease was in infants born between 29 0/7 and 31 6/7 weeks' gestational age without chronic lung disease (decreased from 87% to 21%; P < .001). The second largest absolute decrease was infants born at 32 0/7 to 34 6/7 weeks' gestational age without chronic lung disease and no major anomalies (decreased from 52% to 6%; P < .001). The decrease in term infants with major congenital heart problem was smaller (25 to 17%; P < .001). Even in the most vulnerable infants born between 22 0/7 and 28 6/7 estimated gestational age, palivizumab use declined (88% in 2013 to 74% in 2020; P < .001)., Conclusions: Early AAP guidelines had minor impacts on palivizumab use in infants discharged from the hospital from the NICU. The 2014 guidelines resulted in major changes in palivizumab use and extended into populations for which the AAP guidance remained unchanged., (Copyright © 2022 by the American Academy of Pediatrics.)

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

Introduction: The Bundled Payment for Care Improvement (BPCI) for hip and femur fractures is an effort to increase care quality and coordination at a lower cost. The bundle includes all patients undergoing an operative fixation of a hip or femur fracture (diagnosis-related group codes 480-482). This study aims to investigate variance in the hospital cost and readmission rates for patients within the bundle., Materials and Methods: The study is a retrospective analysis of patients ≥65 years old billed for a diagnosis-related groups 480-482 in 2016 in the National Readmission Database. Cost of admission and length of stay were compared between patients who were or were not readmitted. Regression analysis was used to determine the effects of the primary procedure code and anatomical location of the femur fracture on costs, length of stay, and readmission rates., Results: Patients that were readmitted within 90 days of surgery had an increased cost on initial admission ($18,427 vs $16,844, P < .0001), and an increased length of stay (6.24 vs 5.42, P < .0001). When stratified by procedure, patients varied in readmission rates (20.7% vs 19.6% vs 21.8%), initial cost, and length of stay (LOS). Stratification by anatomical location also led to variation in readmission rates (20.7% vs 18.3% vs 20.6%), initial cost, and LOS., Conclusion: The hip and femur fractures bundle includes a great number of procedures with variance in cost, readmission, and length of stay. This amount of variation may make standardization difficult and may put the hospital at potential financial risk., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Nineteen species of the deep-water fish family Macrouridae inhabit the Mid-Atlantic Ridge (MAR) of the North Atlantic. Size and age structure, longevity and length at age were explored for seven of the more abundant species: Coryphaenoides armatus, Coryphaenoides brevibarbis, Coryphaenoides carapinus, Coryphaenoides guentheri, Coryphaenoides mediterraneus, Coryphaenoides rupestris and Macrourus berglax. The otoliths from these species had growth increments resembling those accepted as annuli in other deep-water species for which validation experiments have been conducted. Based on the counts of these growth increments, age estimates were derived as the basis for studies of age structure, growth and longevity. All the species appeared to have relatively low growth rates, but the interspecific variation in longevity illustrates that there is a considerable variation within the family and among species inhabiting the same deep-sea environment. Most of the species likely complete full life cycles on the MAR, but it is probable that both the youngest and the largest-oldest individuals of some of the species were not sampled adequately., (© 2021 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)

Per- and polyfluoroalkyl substances (PFAS) are contaminants of critical concern due to their persistence, widespread distribution in the environment, and potential human-health impacts. In this work, published studies of PFAS concentrations in soils were compiled from the literature. These data were combined with results obtained from a large curated database of PFAS soil concentrations for contaminated sites. In aggregate, the compiled data set comprises >30,000 samples collected from >2500 sites distributed throughout the world. Data were collected for three types of sites- background sites, primary-source sites (fire-training areas, manufacturing plants), and secondary-source sites (biosolids application, irrigation water use). The aggregated soil-survey reports comprise samples collected from all continents, and from a large variety of locations in both urban and rural regions. PFAS were present in soil at almost every site tested. Low but measurable concentrations were observed even in remote regions far from potential PFOS sources. Concentrations reported for PFAS-contaminated sites were generally orders-of-magnitude greater than background levels, particularly for PFOS. Maximum reported PFOS concentrations ranged upwards of several hundred mg/kg. Analysis of depth profiles indicates significant retention of PFAS in the vadose zone over decadal timeframes and the occurrence of leaching to groundwater. It is noteworthy that soil concentrations reported for PFAS at contaminated sites are often orders-of-magnitude higher than typical groundwater concentrations. The results of this study demonstrate that PFAS are present in soils across the globe, and indicate that soil is a significant reservoir for PFAS. A critical question of concern is the long-term migration potential to surface water, groundwater, and the atmosphere. This warrants increased focus on the transport and fate behavior of PFAS in soil and the vadose zone, in regards to both research and site investigations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Simple Ti imido halide complexes such as [Br 2 Ti(N t Bu)py 2 ] 2 are competent catalysts for the synthesis of unsymmetrical carbodiimides via Ti-catalyzed nitrene transfer from diazenes or azides to isocyanides. Both alkyl and aryl isocyanides are compatible with the reaction conditions, although product inhibition with sterically unencumbered substrates sometimes limits the yield when diazenes are employed as the oxidant. The reaction mechanism has been investigated both experimentally and computationally, wherein a key feature is that the product release is triggered by electron transfer from an η 2 -carbodiimide to a Ti-bound azobenzene. This ligand-to-ligand redox buffering obviates the need for high-energy formally Ti II intermediates and provides further evidence that substrate and product "redox noninnocence" can promote unusual Ti redox catalytic transformations., Competing Interests: The authors declare no competing financial interest.

The mechanism used by the ubiquitin-conjugating enzyme, Ubc13, to catalyze ubiquitination is probed with three computational techniques: Born-Oppenheimer molecular dynamics, single point quantum mechanics/molecular mechanics energies, and classical molecular dynamics. These simulations support a long-held hypothesis and show that Ubc13-catalyzed ubiquitination uses a stepwise, nucleophilic attack mechanism. Furthermore, they show that the first step-the formation of a tetrahedral, zwitterionic intermediate-is rate limiting. However, these simulations contradict another popular hypothesis that supposes that the negative charge on the intermediate is stabilized by a highly conserved asparagine (Asn79 in Ubc13). Instead, calculated reaction profiles of the N79A mutant illustrate how charge stabilization actually increases the barrier to product formation. Finally, an alternate role for Asn79 is suggested by simulations of wild-type, N79A, N79D, and H77A Ubc13: it stabilizes the motion of the electrophile prior to the reaction, positioning it for nucleophilic attack. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

This study described experiences of caregivers of persons with Alzheimer's disease and other dementias (ADRD) and caregivers of persons with other chronic conditions on self-reported health, type of assistance they provide, perceptions of how caregiving interferes with their lives, and perceived level of support. A secondary analysis was conducted of the 2013 Porter Novelli SummerStyles survey data. Of the 4033 respondents, 650 adults self-identified as caregivers with 11.6% caring for people with ADRD. Over half of all caregivers reported that caregiving interfered with their lives to some extent. The greater the perceived support caregivers reported, the less they thought that caregiving interfered with their lives (p < .001). No significant differences were found between ADRD and non-ADRD caregivers regarding general health, types of assistance they provided, and perceived level of support. These findings have the potential to inform future research and practice in the development of supportive services for caregivers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: There are no large studies evaluating pulmonary haemorrhage (PH) in premature infants. We sought to quantify the clinical characteristics, morbidities and mortality associated with early PH., Design: Data were abstracted from the Pediatrix Clinical Data Warehouse, a large de-identified data set. For incidence calculations, we included infants from 340 Pediatrix United States Neonatal Intensive Care Units from 2005 to 2014 without congenital anomalies. Infants <28 weeks' gestation with PH within 7 days of birth were then matched with two controls for birth weight, gestational age, gender, antenatal steroid exposure, day of life 0 or 1 intubation and multiple gestation., Results: From 596 411 total infants, we identified 2799 with a diagnosis of PH. Peak incidence was 86.9 cases per 1000 admissions for neonates born at 24 weeks' gestation. We then identified 1476 infants <28 weeks' gestation with an early PH diagnosis at ≤7 days of age of which 1363 (92.3%) were successfully matched. Patients with early PH had significantly higher exposure to poractant alfa (35.4% vs 28%), diagnosis of shock (63.7% vs 51%) and grade IV intraventricular haemorrhage (20.8% vs 6%). Patients with PH also had significantly higher mortality rates at 7 days of age (40.6% vs 18.9%), 30 days of age (54% vs 28.8%) and prior to discharge (56.9% vs 33.7)., Conclusion: In this large cohort of premature infants, we found PH to be common among the most premature babies. Early PH was associated with significant morbidity and mortality in excess of 50%. A renewed focus on the underlying pathophysiology and prevention of PH is warranted., Competing Interests: Competing interests: VNT has been a consultant for Chiesi USA., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The role of a highly conserved active site asparagine (N79) in the ubiquitin conjugating enzyme, Ubc13, is probed using molecular dynamics simulations. Both wild type and mutant enzymes (N79A and N79D) are studied. Contrary to a popular hypothesis, we show that it is unlikely that N79 stabilizes a reaction intermediate, but instead preferentially hydrogen bonds to a loop near the active site. This keeps the sidechain carboxylate of an aspartate in the loop (D119) near the sidechain amine of the substrate lysine. Our simulations show that this distance increases in the mutants. D119 has been hypothesized to play a variety of roles in the enzyme, including deprotonating the substrate lysine, so changing this distance can have an effect on the enzyme's efficiency. Finally, we show that it is possible for the aspartate to deprotonate the substrate even across long distances if short water wires form that connect the proton donor and acceptor. Short water wires form with greater probability in the wild type than in mutant enzymes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gyrase appears to be the primary cellular target for quinolone antibacterials in multiple pathogenic bacteria, including Bacillus anthracis, the causative agent of anthrax. Given the significance of this type II topoisomerase as a drug target, it is critical to understand how quinolones interact with gyrase and how specific mutations lead to resistance. However, these important issues have yet to be addressed for a canonical gyrase. Therefore, we utilized a mechanistic approach to characterize interactions of quinolones with wild-type B. anthracis gyrase and enzymes containing the most common quinolone resistance mutations. Results indicate that clinically relevant quinolones interact with the enzyme through a water-metal ion bridge in which a noncatalytic divalent metal ion is chelated by the C3/C4 keto acid of the drug. In contrast to other bacterial type II topoisomerases that have been examined, the bridge is anchored to gyrase primarily through a single residue (Ser85). Substitution of groups at the quinolone C7 and C8 positions generated drugs that were less dependent on the water-metal ion bridge and overcame resistance. Thus, by analyzing the interactions of drugs with type II topoisomerases from individual bacteria, it may be possible to identify specific quinolone derivatives that can overcome target-mediated resistance in important pathogenic species.

Objective: Early diagnosis of Alzheimer's disease (AD) or dementia is important so that patients can express treatment preferences, subsequently allowing caregivers to make decisions consistent with their wishes. This study explored the relationship between people's concern about developing AD/dementia, likelihood to be screened/tested, if experiencing changes in cognitive status or functioning, and concerns about sharing the diagnostic information with others., Method: A descriptive study was conducted using Porter Novelli's SummerStyles 2013 online survey data. Of the 6105 panelists aged 18+ who received the survey, 4033 adults responded (response rate: 66%). Chi squares were used with case-level weighting applied., Results: Almost 13% of respondents reported being very worried or worried about getting AD/dementia, with women more worried than men (p<.001), and AD/dementia caregivers more worried than other types of caregivers (p=.04). Women were also more likely than men to agree to be screened/tested if experiencing changes in memory and/or thinking (p<.001). The greater the worry, the more likely respondents would agree to be screened/tested (p<.001). Nearly 66% of respondents were concerned that sharing a diagnosis would change the way others think/feel about them, with women reporting greater concern than men (p=.003)., Conclusion: Findings demonstrate that level of worry about AD/dementia is associated with the reported likelihood that individuals agree to be screened/tested. This information will be useful in developing communication strategies to address public concern about AD/dementia that may increase the likelihood of screening and early detection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Community-academic partnerships have a long history of support from public health researchers and practitioners as an effective way to advance research and solutions to issues that are of concern to communities and their citizens. Data on the development and evaluation of partnerships focused on healthy aging and cognitive health were limited. The purpose of this article is to examine how community partners view the benefits and barriers of a community-academic partner group established to support activities of the South Carolina Healthy Brain Research Network (SC-HBRN). The SC-HBRN is part of the national Healthy Brain Research Network, a thematic research network funded by the Centers for Disease Control and Prevention (CDC). It is focused on improving the scientific and research translation agenda on cognitive health and healthy aging. Semistructured interviews, conducted at end of Year 2 of the 5-year partnership, were used to collect data from partners of the SC-HBRN. Reported benefits of the partnership were information sharing and networking, reaching a broader audience, and humanizing research. When asked to describe what they perceived as barriers to the collaborative, partners described some lack of clarity regarding goals of the network and opportunities to contribute to the partnership. Study results can guide and strengthen other public health-focused partnerships.

The contribution of Charles Thibault in creating and developing a major international centre of animal research at Jouy-en-Josas (near Versailles) in post Second World War France is recorded in detail. Not only did he select a team of gifted young chercheurs, but he stimulated and supported their research in diverse ways. The projects covered were not only primarily of significance to animal reproduction, but they also became relevant to human infertility studies and to IVF treatments. Members of the team in Physiologie Animale gained international research reputations and seasoned overseas researchers were attracted to Jouy-en-Josas for their sabbaticals. Thibault himself was known especially for his studies on the mammalian oocyte, on fertilization both in vivo and in vitro, and for a key publication on parthenogenesis. Over and above leading the department of Physiologie Animale at the Institut National de la Recherche Agronomique (INRA), he was Professor of Reproductive Physiology at the University of Paris VI and an influential member of national committees in Paris. His formal career reached a peak with his appointment as President of the French scientific research organisation (CNRS), and his overall contributions were celebrated both nationally and internationally, not least as Commander of the Legion d'Honneur and recipient of the Wolf Prize, the latter being presented in the Israeli Parliament, the Knessett. His influence continues to be strong, felt in France and beyond through his protégés and his publications.

Community wayfinding becomes more challenging with age and decrements in functioning. Given the growth in numbers of older adults, we need to understand features that facilitate or inhibit wayfinding in outdoor settings to enhance mobility and community engagement. This exploratory study of 35 short- ( n = 14) and long-term ( n = 21) residents in an ethnically diverse neighborhood identified relevant wayfinding factors. Data collection included an interview, map-drawing task, and walk along a previously audited, prescribed route to identify key wayfinding strategies. Most participants sought information from other people as a primary method of route planning. Street signs and landmarks were overwhelming favorites as helpful wayfinding features. When asked to recall the route following the walk, only half of participants gave completely correct directions. Findings reinforce the importance of landmarks and legible, systematic, and consistently available signage, as well as trustworthy person-to-person information sources. Findings also underscore the need for wayfinding research in diverse environments.

This study explored an intensive 3-week training program and use of psychiatric service dogs for military-related posttraumatic stress disorder (PTSD) and associated symptoms. The sample included 2 separate cohorts of military veterans (n = 7 and n = 5) with prior diagnoses of PTSD. Participants completed self-report measures assessing PTSD, depression, perception of social support, anger, and overall quality of life 1 month prior to the training (baseline), at arrival to the training site, and 6-month follow-up. Results indicated that, for this sample, there was a statistically significant decrease in PTSD and depression symptoms from pre- to posttreatment, as well as 6-month follow-up. For most participants decreases were both clinically significant and reliable changes. Further, participants reported significant reductions in anger and improvement in perceived social support and quality of life. Limitations of the study include a lack of control group, a limitation of most naturalistic studies, as well as small sample size. Despite this, the findings indicate that utilizing psychiatric service dogs, coupled with an intensive trauma resilience training program for veterans with ongoing symptoms, is feasible as a complementary treatment for PTSD that could yield beneficial results in terms of symptom amelioration and improvement to overall quality of life. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: Oviducts participate in fertilization and early embryo development, and they are influenced by systemic and local circulation. Local functional interplay between ovary, oviduct and uterus is important, as deduced from the previously observed differences in hormone concentrations, presence of sperm, or patterns of motility in the oviduct after unilateral ovariectomy (UO). However, the consequences of unilateral ovariectomy on the oviductal transcriptome remain unexplored. In this study, we have investigated the consequences of UO in a higher animal model as the pig., Methods: The influence of UO was analyzed on the number of ovulations on the contra ovary, which was increased, and on the ipsilateral oviductal transcriptome. Microarray analysis was performed and the results were validated by PCR. Differentially expressed genes (DEGs) with a fold change ≥ 2 and a false discovery rate of 10 % were analyzed by Ingenuity Pathway Analysis (IPA) to identify the main biofunctions affected by UO., Results: Data revealed two principal effects in the ipsilateral oviduct after UO: i) down-regulation of genes involved in the survival of sperm in the oviduct and early embryonic development, and ii) up-regulation of genes involved in others functions as protection against external agents and tumors., Conclusions: Results showed that unilateral ovariectomy results in an increased number of ovulation points on the contra ovary and changes in the transcriptome of the ipsilateral oviduct with consequences on key biological process that could affect fertility output.

Purpose: Mobility disability is associated with poor lower body function among older adults. This study examines whether specific types of neighborhood characteristics moderate that association., Design and Methods: This study is based on a cross-sectional sample of 884 people aged ≥ 65 years identified through service organizations in Alameda County, CA; Cook County, IL; Allegheny County, PA; and Wake and Durham counties, NC. In-person interviews focus on neighborhood characteristics, physical and cognitive function, depression, and walking. Functional capacity is tested using objective measures of lower body strength, balance, and walking speed. Mobility disability, the main study outcome, is measured as self-reported level of difficulty in walking 2-3 neighborhood blocks. Estimates of main and interactive effects are derived from logistic regression models., Results: Among older adults with poor lower body function, those who report less proximity to goods and services and barriers to walking report more mobility disability than other older adults. In contrast, among older adults with good lower body function, there is a low prevalence of mobility disability and little association between perceptions of the neighborhood and mobility disability., Implications: In addition to more refined longitudinal studies, this research provides a foundation for innovative place-based rehabilitation and hospital discharge programs for older adults newly diagnosed and treated for chronic health conditions., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Preovulatory binding of viable spermatozoa in the oviduct isthmus is widely accepted as a preliminary to fertilization, but details of physiological events associated with epithelial binding and release from binding are themselves little understood. Important questions include the potential number, distribution and stability of such sites in the caudal isthmus, whether multiple molecular forms of binding exist within a single-mated individual, and whether some sites are more favourable than others for the maintenance of preovulatory sperm viability. Also to be resolved is whether spermatozoa interact with the first available binding sites in the isthmus, whether spermatozoa from second or subsequent matings bind closer to the site of fertilization, and whether the first spermatozoa entering the oviduct are those that will be released first with impending ovulation. Ideally, future research needs to focus on a fertilizing spermatozoon monitored in vivo and not on spermatozoa destined to remain on or in the zona pellucida or in the lower reaches of the oviduct.

The use of aqueous film-forming foam (AFFF) to extinguish hydrocarbon-based fires is recognized as a significant source of environmental poly- and perfluoroalkyl substances (PFASs). Although the occurrence of select PFASs in soil and groundwater at former fire-training areas (FTAs) at military installations operable since 1970 has been consistently confirmed, studies reporting the occurrence of PFASs at other AFFF-impacted sites (e.g. emergency response locations, AFFF lagoons, hangar-related AFFF storage tanks and pipelines, and fire station testing and maintenance areas) are largely missing from the literature. Further, studies have mostly focused on a single site (i.e., FTAs at military installations) and, thus, lack a comparison of sites with diverse AFFF release history. Therefore, the purpose of this investigation was to evaluate select PFAS occurrence at non-FTA sites on active U.S. Air Force installations with historic AFFF use of varying magnitude. Concentrations of fifteen perfluoroalkyl acids (PFAAs) and perfluorooctane sulfonamide (PFOSA), an important PFOS precursor, were measured from several hundred samples among multiple media (i.e., surface soil, subsurface soil, sediment, surface water, and groundwater) collected from forty AFFF-impacted sites across ten installations between March and September 2014, representing one of the most comprehensive datasets on environmental PFAS occurrence to date. Differences in detection frequencies and observed concentrations due to AFFF release volume are presented along with rigorous data analyses that quantitatively demonstrate phase-dependent (i.e., solid-phase vs aqueous-phase) differences in the chemical signature as a function of carbon chain-length and in situ PFOS (and to a slightly lesser extent PFHxS) formation, presumably due to precursor biotransformation., (Published by Elsevier Ltd.)

Background: Research on walking and walkability has yet to focus on wayfinding, the interactive, problem-solving process by which people use environmental information to locate themselves and navigate through various settings., Methods: We reviewed the literature on outdoor pedestrian-oriented wayfinding to examine its relationship to walking and walkability, 2 areas of importance to physical activity promotion., Results: Our findings document that wayfinding is cognitively demanding and can compete with other functions, including walking itself. Moreover, features of the environment can either facilitate or impede wayfinding, just as environmental features can influence walking., Conclusions: Although there is still much to be learned about wayfinding and walking behaviors, our review helps frame the issues and lays out the importance of this area of research and practice.

Background: Preventing and/or delaying cognitive impairment is a public health priority. To increase awareness of and participation in behaviors that may help maintain cognitive function or reduce risk of impairment, we need to understand public perceptions about risk and protective factors., Methods: We conducted a scoping review of studies examining the public's perceptions about risk and protective factors related to cognitive health and impairment published since the 2007 National Public Health Road Map to Maintaining Cognitive Health., Results: A search of five databases yielded 1,115 documents published between June 2007 and December 2013. Initial review of abstracts identified 90 potentially eligible studies. After full-article review, 30 met inclusion criteria; four additional articles identified in reference lists also met inclusion criteria. Of the 34, 16 studies addressed Alzheimer's disease (AD) specifically, 15 dementia broadly, 5 mild to moderate cognitive impairment, and 8 normal functioning, with some content overlap. Across studies, respondents reported genetics (n = 14 studies), older age (n = 8), stress (n = 7), brain/head injury (n = 6), and mental illness/brain disease (n = 6) as perceived risk factors for AD and dementia. Protective factors most commonly identified for maintaining cognitive health were intellectual/mental stimulation (n = 13), physical activity (n = 12), healthy diet (n = 10), and social/leisure activities (n = 10)., Conclusions: Studies identified genetics and older age as key perceived risk factors more so than behaviors such as smoking. Individuals perceived that numerous lifestyle factors (e.g. intellectual stimulation, physical activity) could protect against cognitive impairment, AD, and/or dementia. Results can inform national and international education efforts about AD and other dementias.

Gene Expression Microarray technology was used to compare oviduct transcriptome between inseminated and non-inseminated pigs during spontaneous oestrus. We used an in vivo model approaching the study from a physiological point of view in which no hormonal treatment (animals were in natural oestrus) and no artificial sperm selection (selection was performed within the female genital) were imposed. It is therefore emphasised that no surgical introduction of spermatozoa and no insemination at a site other than the physiological one were used. This approach revealed 17 genes that were two-fold or more up-regulated in oviducts exposed to spermatozoa and/or developing embryos and 9 genes that were two-fold or more down-regulated. Functional analysis of the genes revealed that the top canonical pathways affected by insemination were related to the inflammatory response and immune system (Network 1) to molecular transport, protein trafficking and developmental disorder (Network 2) and to cell-to-cell signalling and interaction (Network 3). Some of the genes in network 1 had been previously detected in the oviduct of human and animals, where they were over-expressed in the presence of spermatozoa or pre-implantation embryos (C3, IGHG1, ITIH4, TNF and SERPINE1) whereas others were not previously reported (SAA2, ALOX12, CD1D and SPP1). Genes in Network 2 included RAB1B and TOR3A, the latter being described for the first time in the oviduct and clearly expressed in the epithelial cells of the mucosa layer. Network 3 integrated the genes with the highest down-regulation level (CYP51, PTH1R and TMOD3). Data in the present study indicate a change in gene expression during gamete encounter at the site of fertilization after a natural sperm selection within the female genital tract. These changes would indicate a modification of the environment preparing the oviduct for a successful fertilization and for an adequate embryo early development.

There is a critical need to develop appropriate management strategies for 1,4-dioxane (dioxane) due to its widespread occurrence and perceived recalcitrance at groundwater sites where chlorinated solvents are present. A comprehensive evaluation of California state (GeoTracker) and Air Force monitoring records was used to provide significant evidence of dioxane attenuation at field sites. Temporal changes in the site-wide maximum concentrations were used to estimate source attenuation rates at the GeoTracker sites (median length of monitoring period = 6.8 years). While attenuation could not be established at all sites, statistically significant positive attenuation rates were confirmed at 22 sites. At sites where dioxane and chlorinated solvents were present, the median value of all statistically significant dioxane source attenuation rates (equivalent half-life = 31 months; n = 34) was lower than 1,1,1-trichloroethane (TCA) but similar to 1,1-dichloroethene (1,1-DCE) and trichloroethene (TCE). Dioxane attenuation rates were positively correlated with rates for 1,1-DCE and TCE but not TCA. At this set of sites, there was little evidence that chlorinated solvent remedial efforts (e.g., chemical oxidation, enhanced bioremediation) impacted dioxane attenuation. Attenuation rates based on well-specific records from the Air Force data set confirmed significant dioxane attenuation (131 out of 441 wells) at a similar frequency and extent (median equivalent half-life = 48 months) as observed at the California sites. Linear discriminant analysis established a positive correlation between dioxane attenuation and increasing concentrations of dissolved oxygen, while the same analysis found a negative correlation with metals and CVOC concentrations. The magnitude and prevalence of dioxane attenuation documented here suggest that natural attenuation may be used to manage some but not necessarily all dioxane-impacted sites.

Physical and cognitive limitations often accompany aging, increasing the importance of a safe and supportive environment to help older adults maintain mobility. Neighborhood design and maintenance must be evaluated to promote physical activity, mobility, and safety. Audit tools, geographic information system data, and resident interviews are used for this purpose, but often fail to provide information that can be translated to practice. The current project is part of a larger Miami-Dade Age-Friendly Initiative to create a metropolitan area that fosters a healthy environment for diverse adults of all ages and abilities. Safe Routes uses a toolkit based on the 5-E model providing practical resources to guide stakeholders in meeting the needs of the community. Findings include the Centers for Disease Control Healthy Aging Research Network Audit Tool assessment for environmental walkability factors. Results from street segment audits along with input from residents can be used to inform sound environmental policies., (Copyright 2015, SLACK Incorporated.)

Objectives: We explored relationships between depressive symptoms and neighborhood environment measures including traffic safety, crime, social capital, and density of businesses in community-dwelling older adults from four different regions of the United States., Method: The Healthy Aging Research Network walking study is a cross-sectional study of 884 adults aged 65+, which included a 10-item Center for Epidemiologic Studies Depression scale of depressive symptoms, demographics, self-reported neighborhood perceptions, and objective neighborhood data., Results: After adjusting for individual covariates, reports of neighborhood crime, unsafe traffic, and unwillingness of neighbors to help each other were significantly positively associated with depressive symptoms among participants., Conclusion: This research suggests an association between self-reported depressive symptoms and the social and built environment; examining causal association requires additional longitudinal research in diverse populations of older adults.

Coordination between the N-terminal gate and the catalytic core of topoisomerase II allows the proper capture, cleavage, and transport of DNA during the catalytic cycle. Because the activities of these domains are tightly linked, it has been difficult to discern their individual contributions to enzyme-DNA interactions and drug mechanism. To further address the roles of these domains, we analyzed the activity of the catalytic core of human topoisomerase IIα. The catalytic core and the wild-type enzyme both maintained higher levels of cleavage with negatively (as compared to positively) supercoiled plasmid, indicating that the ability to distinguish supercoil handedness is embedded within the catalytic core. However, the catalytic core alone displayed little ability to cleave DNA substrates that did not intrinsically provide the enzyme with a transport segment (i.e., substrates that did not contain crossovers). Finally, in contrast to interfacial topoisomerase II poisons, covalent poisons did not enhance DNA cleavage mediated by the catalytic core. This distinction allowed us to further characterize the mechanism of etoposide quinone, a drug metabolite that functions primarily as a covalent poison. Etoposide quinone retained some ability to enhance DNA cleavage mediated by the catalytic core, indicating that it still can function as an interfacial poison. These results further define the distinct contributions of the N-terminal gate and the catalytic core to topoisomerase II function. The catalytic core senses the handedness of DNA supercoils during cleavage, while the N-terminal gate is critical for capturing the transport segment and for the activity of covalent poisons.

Mobility, broadly defined as movement in all of its forms from ambulation to transportation, is critical to supporting optimal aging. This article describes two projects to develop a framework and a set of priority actions designed to promote mobility among community-dwelling older adults. Project 1 involved a concept-mapping process to solicit and organize action items into domains from a broad group of stakeholders to create the framework. Concept mapping uses qualitative group processes with multivariate statistical analysis to represent the ideas visually through maps. A snowball technique was used to identify stakeholders (n = 211). A 12-member steering committee developed a focus prompt, "One specific action that can lead to positive change in mobility for older adults in the United States is..." Project 2 included a Delphi technique (n = 43) with three iterations to prioritize four to six items using results from the concept mapping rating process. Project 1 resulted in 102 items across nine domains (Research to Practice, Independence and Engagement, Built Environment and Safety, Transportation, Policy, Housing and Accessibility, Community Supports, Training, and Coordinated Action). The number of items ranged from 6 to 18 per domain. Project 2 resulted in agreement on four items that reflect the importance of promoting environmental strategies through collaborative initiatives aimed at planning and best practices focusing on environmental enhancements or transit, training of professionals, and integration of mobility into state and local public health plans. These findings can be applied to support coordinated, multidisciplinary research and practice to promote mobility among older adults., (© 2014 Society for Public Health Education.)

The organophosphorus insecticide chlorpyrifos has been widely used. Its active metabolite chlorpyrifos-oxon (CPO) is a potent anticholinesterase and is detoxified by paraoxonase 1 (PON1). PON1 activity is influenced by numerous factors including a Q192R polymorphism. Using forty human blood samples bearing homozygous genotypes and either high or low activity phenotypes (as determined by high concentration assays of paraoxon and diazoxon hydrolysis) the serum PON1 hydrolysis of high (320 μM) and low (178 nM) CPO concentrations was assessed using direct or indirect spectrophotometric methods, respectively. PON1 activity at high CPO concentration reflected the phenotype and genotype differences; subjects with the high activity phenotype and homozygous for the PON1R192 alloform hydrolyzed significantly more CPO than subjects with the low activity phenotype and/or PON1Q192 alloform (high RR=11023±722, low RR=9467±798, high QQ=8809±672, low QQ=6030±1015 μmol CPO hydrolyzed/min/L serum). However, PON1 hydrolysis of CPO at the lower, more environmentally relevant concentration showed no significant differences between the PON1192 genotypes and/or between high and low activity phenotypes (high RR=231±27, low RR=219±52, high QQ=193±59, low QQ=185±43 nmol CPO/min/L serum). Low CPO concentrations were probably not saturating, so PON1 did not display maximal velocity and the PON1 genotype/phenotype might not influence the extent of metabolism at environmental exposures., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This essay proposes that highly localized communication between free and bound spermatozoa in the caudal portion of the oviduct acts to regulate the numbers detaching from the epithelium and progressing to the site of fertilization close to the time of ovulation. Low initial sperm:egg ratios are essential for monospermic fertilization. Liberation of surface macromolecules and metabolic prompting from activated spermatozoa, together with altered patterns of sperm movement and dynamic differences in intracellular Ca(2+) ion status between neighboring sperm cells, would influence the progressive release of spermatozoa from the reservoir in the oviduct isthmus. Different intensities of preovulatory epithelial binding, reflecting a range of states in the sperm surface membranes and associated proteins, would provide a further explanation for a chronologically staggered periovulatory detachment of spermatozoa. Intimate sperm-sperm interactions within the confines of the oviduct isthmus offer a sensitive means of fine-tuning the vanguard of competent male gametes reaching the isthmo-ampullary junction., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Type II topoisomerases are essential enzymes that modulate DNA under- and overwinding, knotting, and tangling. Beyond their critical physiological functions, these enzymes are the targets for some of the most widely prescribed anticancer drugs (topoisomerase II poisons) in clinical use. Topoisomerase II poisons kill cells by increasing levels of covalent enzyme-cleaved DNA complexes that are normal reaction intermediates. Drugs such as etoposide, doxorubicin, and mitoxantrone are frontline therapies for a variety of solid tumors and hematological malignancies. Unfortunately, their use also is associated with the development of specific leukemias. Regimens that include etoposide or doxorubicin are linked to the occurrence of acute myeloid leukemias that feature rearrangements at chromosomal band 11q23. Similar rearrangements are seen in infant leukemias and are associated with gestational diets that are high in naturally occurring topoisomerase II-active compounds. Finally, regimens that include mitoxantrone and epirubicin are linked to acute promyelocytic leukemias that feature t(15;17) rearrangements. The first part of this article will focus on type II topoisomerases and describe the mechanism of enzyme and drug action. The second part will discuss how topoisomerase II poisons trigger chromosomal breaks that lead to leukemia and potential approaches for dissociating the actions of drugs from their leukemogenic potential., (© 2014 New York Academy of Sciences.)

The 1st Puerto Rico Biobanking Workshop took place on August 20st, 2014 in the Auditorium of the Comprehensive Cancer Center of the University of Puerto Rico, Medical Sciences Campus in San Juan Puerto Rico. The program for this 1-day, live workshop included lectures by three biobanking experts, followed by presentations from existing biobanks in Puerto Rico and audience discussion. The need for increasing biobanking expertise in Puerto Rico stems from the fact that Hispanics in general are underrepresented in the biobanks in existence in the US, which limits the research conducted specifically to understand the molecular differences in cancer cells compared to other better studied populations. In turn, this lack of information impairs the development of better diagnostic and therapeutic approaches for our population. Dr. James Robb, M.D., F.C.A.P., consulting pathologist to the National Cancer Institute (NCI) and the Office of Biorepositories and Biospecimen Research (OBBR), opened the workshop with a discussion on the basic aspects of the science of biobanking (e.g., what is a biobank; its goals and objectives; protocols and procedures) in his talk addressing the importance of banking tissues for advancing biomedical research. Next, Dr. Gustavo Stefanoff, from the Cancer Institutes Network of Latin America (RINC by its name in Spanish), explained the mission, objectives, and structure of the Network of Latin-American and Caribbean Biobanks (REBLAC by its name in Spanish), which despite limited resources and many challenges, currently accrue high quality human tissue specimens and data to support cancer research in the region. Dr. Robert Hunter-Mellado, Professor of Internal Medicine, Universidad Central del Caribe, followed with an examination of the ethical and regulatory aspects of biobanking tissues for future research, including informed consent of subjects; protection of human subjects rights; and balancing risks and benefit ratios. In the afternoon, the directors of existing biobanks in Puerto Rico (the Puerto Rico Biobank, the Comprehensive Cancer Center biobank, and an HIV-focused biobank at Universidad Central del Caribe) presented their experiences and challenges with establishing biobanks for research in Puerto Rico. In sum, this workshop presented opportunities to share knowledge in the science of biobanking, for further training, and of networking among the participants (34 from 4 different institutions), which will strengthen the collaborative links between investigators studying cancer in Latin America, the Caribbean, and the US.

This article reviews the remarkable life and major scientific achievements of the reproductive biologist M.C. Chang. His scholarly career progressed from university in Peking, via Edinburgh, Scotland, and Cambridge, England, to the newly founded Worcester Foundation for Experimental Biology in Massachusetts. At each stage, the hand of fate is noted as are the support and encouragement of key professors. Chang's own contributions on capacitation of spermatozoa, in vitro fertilisation of mammalian eggs, and transplantation of oocytes and embryos are all brought out, as is his essential input to the creation and development of a steroid contraceptive pill. He strongly encouraged young reproductive biologists who worked in his laboratory, and applauded the world-wide distinction of his student and associate, R. Yanagimachi, as a specialist in mammalian fertilisation. Finally, Chang's continued feelings towards his homeland are contrasted with the reality of his American life after 1945, itself a study in poignancy.

Safe and well-designed community environments support healthful behaviors that help prevent chronic conditions and unintentional injuries and enable older adults to be active and engaged in community life for as long as possible. We describe the work of the Healthy Aging Research Network (HAN) and partners over the past decade to better understand place-based determinants of health and translate that knowledge to real-world practice, with a focus on environmental strategies. Using key components of the Knowledge to Action framework, we document the importance of a sustained, multidisciplinary, collaborative approach and ongoing interaction between researchers and communities. We share examples of practical tools and strategies designed to engage and support critical sectors with the potential to enhance the health and well-being of older adults and their communities. We conclude with a description of lessons learned in facilitating the translation of prevention research into practice.

The prevalence of food allergies in the inmate population is a relatively unknown and perhaps underreported health issue. An inmate with an undetected food allergy is at risk for anaphylaxis or less serious complications and is becoming an increasing concern to correctional facilities. Allergic responses to foods cause many symptoms, including cutaneous, gastrointestinal, respiratory, cardiovascular, and anaphylactic. These nonspecific symptoms are often first thought to be related to other conditions. Cell-mediated disorders, food intolerances, and pharmacologic conditions should be considered in the differential diagnosis and appropriately ruled out. The symptoms may mimic other problems, and allergic reactions would not be among the first conditions considered in the differential diagnosis. Consideration of food allergies and recognition of the symptoms should prompt a diagnostic evaluation. Not all correctional institutions have access to a dietitian or conduct allergy testing and the need to prepare special meals may create challenges.

Deep body temperature in mammals is generally but incorrectly regarded as uniform. Alterations of temperature in oviducts and preovulatory Graafian follicles may play a vital role in gamete maturation, fertilization and early embryonic development. At a molecular level, the conformation of regulatory proteins is susceptible to changes in temperature. Deviation from physiological temperature during IVF procedures could thereby exert a profound influence on patterns of gene expression as the embryonic genome unfolds during early cleavage stages and act to generate specific anomalies. Systematic studies are urgently required. The temperature of internal body organs in mammals such as rabbits and humans is widely regarded as uniform, but this is not correct. Temperatures in reproductive tissues such as ovaries and oviducts vary according to the stage of a menstrual or oestrous cycle. Such changes in temperature are thought to be critically involved in the maturation of eggs and spermatozoa and thus in events shortly before and after fertilization. Proteins in the cytoplasm and nuclei of eggs and very young embryos respond to small shifts in temperature by changing their three-dimensional shape. Conformational modifications in regulatory proteins in the nucleus would influence patterns of gene expression in developing embryos and may, when perturbed, alter the sexual phenotype of an individual. In the practical context of IVF, studies are needed of the influence of culturing gametes and embryos at different temperatures and ranges of temperature on the patterns of gene expression in preimplantation embryos., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Paramount to staging and patient management is accurately measuring the size of invasive breast cancers. We assessed the accuracy of mammography (MG), ultrasonography (US), and magnetic resonance imaging (MRI) at our community-based hospital in which multiple radiologists and imaging machines are used in the care of our patients. We performed a retrospective analysis of a prospectively maintained database of 277 patients seen at our breast center from 2009 to 2010. We tabulated MG, US, and MRI-reported tumor sizes in 161 women with pathology-proven invasive breast cancer and compared the preoperative size measurements with final pathologic tumor size. In the 161 patients, 169 lesions were identified. Imaging using all three modalities was available in 47 patients. When compared with final pathology, MRI had a correlation of r = 0.75 to mean tumor size as compared with US (r = 0.67) and MG (r = 0.76). Mean tumor size was 1.90 cm by MG, 1.87 cm by US, 2.40 cm by MRI, and 2.19 cm by pathology. We were able to achieve an excellent correlation of pathologic tumor size to preoperative imaging. The absolute differences in size between the modalities were small. MRI, in select patients, added to the assessment of tumor size based on US and MG.

Recalling the evolutionary sequence of development first of gonad and subsequently of oviducts, ovarian endocrine regulation of all known components of oviduct physiology is reviewed. Ovaries not only influence oviducts via the systemic blood circulation, but also locally by counter-current transfer of relatively high concentrations of steroid hormones and prostaglandins between the ovarian vein and oviduct branch of the ovarian artery. The efficiency and impact of such counter-current transfer is greatest around the time of ovulation, the transfer process receiving further inputs from hormones present in peritoneal fluid. Classical oviduct physiology is summarised, and the potential molecular consequences of temperature gradients within the duct lumen examined. At ovulation, an oocyte-cumulus complex is displaced in minutes from the follicular surface to the site of fertilisation at the ampullary-isthmic junction of the oviduct. This rapid initial phase is contrasted with the subsequent slow progression of embryos to the uterus in days, still encompassed within a zona pellucida. Regarding transport of spermatozoa, the formation of a pre-ovulatory reservoir in the caudal portion of the oviduct isthmus is noted, with suppression of motility and sperm-head binding to epithelial organelles acting to maintain fertilising ability. Completion of capacitation is prompted shortly before ovulation, predominantly by Ca(2+) influx into bound spermatozoa. A controlled release of spermatozoa coupled with their hyperactivation results in initial sperm:egg ratios at the site of fertilisation close to unity, thereby avoiding the pathological condition of polyspermy. Both the oviduct milieu and embryonic development are influenced by paracrine activity of follicular granulosa cells released at ovulation and remaining in suspension in the vicinity of the oocyte or embryo. These cells may amplify early pregnancy signals from a zygote to the endosalpinx. Beneficial effects of the oviduct on domestic animal embryos are contrasted with anomalies arising as a consequence of in vitro culture. Primate embryos do not require exposure to an oviduct for normal development, perhaps due to overlapping compositions of endosalpingeal and endometrial secretions. Additionally, primate endometrial secretions may be modified by viable gametes or an embryo in the presence of a cumulus cell suspension., (© 2011 The Author. Biological Reviews © 2011 Cambridge Philosophical Society.)