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This article is the publication of an indurated limestone standing statue, now in Montrose Museum (ANGUSalive M1980.4578), identified as a Sistrum-player. The statue was collected in 1834 by Dr James Burnes IV, a relative of the Scottish poet Robert Burns, during a journey from India to Scotland. Stylistic features of the statue and its inscription are discussed here for the first time. Her family tree is also reconstructed based on known objects in international collections, restoring her to an important Theban priestly family of the early Ptolemaic Period, which is the largest yet proposed family tree for this group. This is followed by a discussion of the attested individuals.

A novel coronavirus has had global impact on individual health and health care delivery. In this C4 article, contributors discuss various aspects of transplantation including donor and recipient screening, management of infected patients, and prevention of coronavirus disease (COVID). Donor screening with SARS-CoV-2 nucleic acid testing (NAT) close to the time of procurement is recommended. Many programs are also screening all potential recipients at the time of admission. The management of COVID has evolved with remdesivir emerging as a new potential option for transplant recipients. Dexamethasone has also shown promise and convalescent plasma is under study. Prevention strategies for transplant candidates and recipients are paramount. Pediatric-specific issues are also discussed. Strategies for the psychological well-being of patients and providers are also imperative, in addition to future research priorities for transplantation.

This cross-sectional study examines the postintensive care syndrome in patients who had vs patients who had not resumed driving 1 month after hospitalization for a critical illness.

Medicare Part D plans make coverage decisions according to FDA-labeled indications and off-label uses endorsed by two CMS-recognized compendia. Patients who rely on Medicare Part D for immunosuppressive drug coverage are at risk for denied coverage when these medications are prescribed off-label. The purpose of this multicenter collaboration was to assemble a case series documenting situations where immunosuppressive therapies prescribed for transplant patients were denied by Medicare Part D prescription drug plans. This case series documents 66 instances in 39 patients where immunosuppressive drug claims were denied coverage due to off-label use not endorsed by the compendia. Patients were recipients of lung (n = 28, 72%), heart (n = 7, 18%), or liver (n = 4, 10%) transplants. Denied claims were for mycophenolate mofetil (n = 22, 33%), azathioprine (n = 18, 27%), sirolimus (n = 15, 23%), mycophenolate sodium (n = 5, 8%), everolimus (n = 5, 8%), and belatacept (n = 1, 1%). Most denials were upheld across all the levels of attempted appeal, including those escalated to a Medicare Administrative Law Judge. This case series demonstrates a critical flaw in the construct of the Medicare Prescription Drug Benefit. The currently referenced compendia are not up to date and do not reflect best practices in organ transplantation.

Heroin intake decreases during the proestrus phase of the estrous cycle in female rats. Circulating concentrations of both estradiol and progesterone peak during proestrus, and it is not known which of these hormones, or their combination, are responsible for these effects. The purpose of this study was to determine the effects of estradiol, progesterone, and their combination on heroin self-administration in female rats. In Experiment 1, the estrous cycle of intact female rats was tracked daily. If a rat was in proestrus, either the estrogen-receptor antagonist, raloxifene, the progesterone-receptor antagonist, mifepristone, or their combination was administered 30 minutes prior to a heroin self-administration session. In this experiment, raloxifene, but not mifepristone, significantly blocked proestrus-associated decreases in heroin intake. In Experiment 2, separate groups of ovariectomized female rats were treated chronically with exogenous estradiol, progesterone, estradiol + progesterone, or vehicle, and heroin intake was examined over a 100-fold dose range. In this experiment, estrogen-treated rats self-administered less heroin than any other group and significantly less heroin than rats treated with progesterone. These data suggest that (1) estradiol but not progesterone is responsible for proestrus-associated decreases in heroin intake and (2) estradiol decreases heroin intake relative to progesterone. These data differ from those reported previously with stimulants and suggest that estrogen-based pharmacotherapies may be of value to women with opioid use disorder.

Background and objectives: An active and engaged lifestyle is supported as being beneficial for brain health. Activities comprising physical, mental and social demands, or combinations of those, are of particular interest, and have been the focus of specific interventions. Exploring how older people engage with such community-based activities, including facilitators and barriers to participation, may help improve the success of future translational activities. Research design and methods: Twenty-seven older adults aged 65-86 (56% female) who had completed an activity-based intervention study participated in three focus groups. Discussions explored their experiences of taking up a new activity, including facilitators and barriers to their engagement, and their perceptions of any benefits.Results: Thematic analysis grouped participants’ responses into five themes: positive aspects and facilitators of engagement in a new activity; challenges and barriers to engagement; ageing being a facilitator and a barrier to engagement; differential effects of activities on participants’ health and wellbeing; and general project feedback (including opinions on study design). Discussion and implications: Participants’ experiences and expectations included positive (e.g., enjoyment, socialisation) and negative factors (e.g., lack of confidence, other commitments, class costs and poor structure), consistent with previous research on social participation and engaging with new learning opportunities. Future studies should also consider those who do not readily participate in leisure activities to address earlier barriers. It is important that older adults have access to potentially beneficial activities and local authorities should prioritise increasing their provision.

Troponins are proteins that are integral components of the contractile mechanism of muscle, including cardiac muscle. Cardiac troponins Iand T can be detected in the blood of most people after puberty, at concentrations reflecting cardiac mass, sex and age. Current laboratory assays are approximately 1000 times more sensitive than those used previously. They also have higher sensitivity than point-of-care assays. The measurement of cardiac troponins is used primarily to assist in the diagnosis or exclusion of myocardial injury. Serial tests in acute coronary syndrome are guided by the Universal Definition of Myocardial Infarction.

Background The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use. We report the impact of core elements implementation within Veterans Health Administration sites. Methods In this quasiexperimental controlled study, effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARIs) were assessed. Outcomes included per-visit antibiotic prescribing, treatment appropriateness, ARI revisits, hospitalization, and ARI diagnostic changes over a 3-year pre-implementation period and 1-year post-implementation period. Logistic regression adjusted for covariates (odds ratio [OR], 95% confidence interval [CI]) and a difference-in-differences analysis compared outcomes between intervention and control sites. Results From 2014–2019, there were 16 712 and 51 275 patient visits within 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre- and post-implementation within intervention sites were 59.7% and 41.5%, compared to 73.5% and 67.2% within control sites, respectively (difference-in-differences, P < .001). Intervention site pre- and post-implementation OR to receive appropriate therapy increased (OR, 1.67; 95% CI, 1.31–2.14), which remained unchanged within control sites (OR,1.04; 95% CI, .91–1.19). ARI-related return visits post-implementation (–1.3% vs –2.0%; difference-in-differences P = .76) were not different, but all-cause hospitalization was lower within intervention sites (–0.5% vs –0.2%; difference-in-differences P = .02). The OR to diagnose non-specific ARI compared with non-ARI diagnoses increased post-implementation forintervention (OR, 1.27; 95% CI, 1.21 –1.34) but not control (OR, 0.97; 95% CI, .94–1.01) sites. Conclusions Implementation of the core elements was associated with reduced antibiotic prescribing for RIs and a reduction in hospitalizations. Diagnostic coding changes were observed.

Background Reference intervals are an important aid in medical practice as they provide clinicians a guide as to whether a patient is healthy or diseased. Outlier results in population studies are removed by any of a variety of statistical measures. We have compared several methods of outlier removal and applied them to a large body of analytes from a large population of healthy persons. Methods We used the outlier exclusion criteria of Reed-Dixon and Tukey and calculated reference intervals using nonparametric and Harrell-Davis statistical methods and applied them to a total of 36 different analytes. Results Nine of 36 analytes had a greater than 20% difference in the upper reference limit, and for some the difference was 100% or more. Conclusions For some analytes, great importance is attached to the reference interval. We have shown that different statistical methods for outlier removal can cause large changes to reported reference intervals. So that population studies can be readily compared, common statistical methods should be used for outlier removal.

Background. Although women are informed about the dangers of drinking and smoking during pregnancy when they book for antenatal care, it is uncertain whether this advice is accepted, or whether attempts are made to apply it in subsequent pregnancies. Objectives. To assess how pregnant women respond to the advice to refrain from smoking and drinking during pregnancy in subsequent pregnancies. Methods. Research staff were trained to obtain accurate prospective information on smoking and drinking during pregnancy in a prospective study, using well-standardised methods. Care was taken to inform participants about the dangers of smoking and drinking during pregnancy. They were also given pamphlets on these dangers in their own language and a list of telephone numbers where they could find help to quit should they need it. This information was repeated at subsequent study visits (ranging from 1 to 3, depending on the gestational age at which they enrolled). Gestational age was determined by early ultrasound. Z -scores of birthweight for gestational age were determined according to the INTERGROWTH-21st study. Pregnancy outcomes of women who enrolled twice ( n =888) or three times ( n =77) in the Safe Passage Study were compared with those of women in the first enrolment ( n =889). Results. The proportion of drinkers did not change significantly ( p =0.058) from the first to the second and third enrolments (63.8%, 59.0% and 54.6%, respectively). A similar trend was found for smokers (73.3%, 72.2% and 68.4%, respectively). Cannabis use was reported by 15.1%, 9.7% and 12.0% ( p

Supplemental Digital Content is available in the text., Objective: Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. Approach and Results: We used a novel ApoE−/− knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions—pravastatin and minocycline—had distinct anti-inflammatory effects at the plaque and systemic level. Conclusions: We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagen-poor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.

Inhibition of members of the bromodomain and extraterminal (BET) family of proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 and BD2) that are necessary for recognition of acetylated lysine residues in the N-terminal regions of histones. Chemical matter that targets BET (BETi) also interact via these domains. Molecular and cellular data indicate that BD1 and BD2 have different biological roles depending upon their cellular context, with BD2 particularly associated with cancer. We have therefore pursued the development of BD2-selective molecules both as chemical probes and as potential leads for drug development. Here we report the structure-based generation of a novel series of tetrahydroquinoline analogs that exhibit >50-fold selectivity for BD2 versus BD1. This selective targeting resulted in engagement with BD-containing proteins in cells, resulting in modulation of MYC proteins and downstream targets. These compounds were potent cytotoxins toward numerous pediatric cancer cell lines and were minimally toxic to nontumorigenic cells. In addition, unlike the pan BETi (+)-JQ1, these BD2-selective inhibitors demonstrated no rebound expression effects. Finally, we report a pharmacokinetic-optimized, metabolically stable derivative that induced growth delay in a neuroblastoma xenograft model with minimal toxicity. We conclude that BD2-selective agents are valid candidates for antitumor drug design for pediatric malignancies driven by the MYC oncogene. Significance: This study presents bromodomain-selective BET inhibitors that act as antitumor agents and demonstrates that these molecules have in vivo activity towards neuroblastoma, with essentially no toxicity.

OBJECTIVE Preanalytical processing of blood samples can affect plasma glucose measurement because ongoing glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood samples for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined. RESEARCH DESIGN AND METHODS All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT samples in NaF tubes were centrifuged within 10 min (early centrifugation). RESULTS A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h, and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P < 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887). CONCLUSIONS The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood samples used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.

Several studies suggest that the perirhinal cortex (PER) may function to unitize stimulus components across time or modalities. While the PER has been shown to be critical for fear acquisition to discontinuous stimuli, the role of the PER in fear extinction memory has not been evaluated. The current study assessed the involvement of the PER during fear extinction training to a continuous or discontinuous conditioned stimulus (CS). Rats were randomly assigned to 1 of 4 groups based on 2 factors: the CS type (a continuous or discontinuous light) and a pretesting PER manipulation (muscimol inactivation or saline). Results showed that PER inactivation impaired fear memory to both CS types; however, PER inactivation had only impaired extinction memory to the discontinuous light. These results suggest the role of the PER in stimulus unitization extends to supporting the acquisition of fear extinction memory. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

AbstractReforestation and restoration efforts have traditionally relied on “local” seed sources as planting stock. The term “local” has different meanings in different locales, since no single set of seed-collection zones has yet been widely adopted across the eastern United States. Given concerns about mitigating the effects of climate change, forest managers are increasingly seeking to move seed sources in a process called assisted migration, which would be facilitated if a common set of seed-collection zones were available. We developed a map of 245 seed-collection zones for 37 states by combining two ecologically important layers: plant hardiness zones and ecoregions. These new seed-collection zones should be used by seed collectors and nurseries to describe the origin of seed for plants and trees in the eastern United States. Common garden studies remain the gold standard for determining how far to move seed from any particular seed-collection zone. For species that have not been field-tested, seed movement that is limited either within a seed-collection zone or between adjacent seed-collection zones is a reasonable general guideline.

Objectives Knowing the intra-individual variation (CVi), also termed within subject biological variation, of an analyte is essential to properly interpret apparent changes in concentration. While there have been many studies assessing the CVi of cardiac troponin (cTnI), they have been limited in looking at CVi in different settings, and there is no data available on whether CVi might change in different settings. Methods We used our large cTnI data bank to look at the CVi of cTnI in Emergency Department (ED) patients who had an acute myocardial infarction event excluded. We looked at the effects of gender, age, climatic season, and time between samples to assess whether CVi changed. To assess the effect of age, after exclusion, we collected two samples from each subject for each study which were used to calculate the CVi between those identified groups. There were 139 males and 98 females aged Results For the four variables listed, there were no significant differences in within individual variation (CVi), but there was a significant difference in between individual variation (CVg) for men and women with regard to age. The Index of Individuality (II) was 90% of subjects had an reference change value (RCV) Conclusions Because troponin concentration in patients without an identified cardiac condition change so little, delta changes are potentially of great value in assessing patients in the ED. Significant delta changes in troponin can occur without the 99th percentile being exceeded.

Background The importance of physical activity in early childhood for establishing long-term health is well understood, yet with the exception of recent WHO guidelines, public health initiatives rarely focus on children below school age. Moreover, little is known about how domestic spaces and day-to-day caring activities influence preschool-age children's physical activity. To examine this, we explore caregivers' perceptions of young children's activities within and outside the home, and we consider how lived experiences of caregiving align (or not) with current physical activity policy. Methods Semi-structured interviews with 49 parents and grandparents from 16 families were conducted in Oregon, USA; each family had a child aged 3–5 years. Questions focused on caregivers' perceptions of and involvement with children's body weights, activities, and food practices. The interviews were analysed using thematic analysis. Our analysis drew on a materialities framework, attending to relationships between children, caregivers, spaces in and around the home, and everyday activities. Results Four themes were developed: appropriateness of outside versus inside spaces for physical activity; making accommodations for physical activity in the home; active spaces of care, referring to relationships among space, activity type, and caregiver attention; and mundane movement, or the low-intensity movement of everyday life. Together, the results highlight that children's day-to-day activities cut across a spectrum of movement, mediated by available spaces and caregiving affordances. Conclusions Attending to the full spectrum of children's movements highlights how children's activities interlink with family routines, available indoor and outdoor spaces, and the intended uses of these spaces. These interplays between space, care, and physical activity enacted at the household level should inform an integrated, systems-level public health approach to increasing health and well-being for preschool-age children. Suggestions for improvement include coordinating policy development across multiple fields (e.g., housing design, urban planning) that structure the activities of children and their caregivers across ‘home’ and ‘outside’ spaces.

Purpose Existing research has highlighted the need for influential leaders to respond to the evolving social, economic and environmental constraints on the construction industry. Studies on leadership in other sectors have shown that influential leaders tend to demonstrate a high level of emotional intelligence. Little or no research examining relationships between leadership style and emotional intelligence has been conducted specific to construction project managers. This study aims to identify the prevalent leadership style adopted by construction project managers and investigate potential correlations between leadership style and emotional intelligence. Design/methodology/approach An online questionnaire including a mix of open and closed questions was adopted to address the research objectives. The group studied comprised project managers currently working in the construction industry in New Zealand and the UK. Findings The research found that transformational leadership style is prevalent among project managers examined in this study. Significant positive relationships were found between project managers’ emotional intelligence and their likelihood of adopting a transformational leadership style. Originality/value The research results provide the construction industry with a benchmark against which individuals with high emotional intelligence, and so most suited to the challenges of the project management role, can be identified and trained. Recommendations including suitable methods for identifying, recruiting and training project managers, as well as secondment and mentoring options, were suggested for improving leadership capabilities in the construction industry.

Pests (e.g., insects, pathogens) affect forest communities through complex interactions with plants, other animals, and the environment. While the effects of exotic (non-native) pests on trees received broad attention and were extensively studied, fewer studies addressed the ecosystem-level consequences of these effects. Related studies so far mostly only targeted a very few dominant pests (e.g., hemlock woolly adelgid—HWA, beech bark disease—BBD, and spongy moth—SM) and were limited to aspects of the complex situation such as (1) pests’ direct physical disturbance to forest ecosystems, (2) altered geochemical elements of soils, water, and air (e.g., excretion), and (3) feedback effects from the alteration of ecosystems on plants, native insects, and present and future pest invasions. New studies also show that, in general, planted forests appear to be more prone to exotic pest invasions and thus suffer greater impacts than natural forests. Integrated studies are critically needed in the future to address (1) direct/indirect interactions of pests with ecosystem elements, (2) both short- and long-term effects, and (3) feedback effects. We discuss the implications of the new findings and corresponding management strategies.