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Introduction: Abdominal pain is one of the most frequent reasons for an emergency department (ED) visit. Most cases are functional and no therapy has proven effective. Our objective was to determine if hyoscine butylbromide (HBB) (BuscopanTM) is effective for children who present to the ED with functional abdominal pain. Methods: We conducted a randomized, blinded, superiority trial comparing HBB 10 mg plus acetaminophen placebo to oral acetaminophen 15 mg/kg (max 975 mg) plus HBB placebo using a double-dummy approach. We included children 8-17 years presenting to the ED at London Health Sciences Centre with colicky abdominal pain rated >40 mm on a 100 mm visual analog scale (VAS). The primary outcome was VAS pain score at 80 minutes post-administration. Secondary outcomes included adverse effects; caregiver satisfaction with pain management using a five-item Likert scale; recidivism and missed surgical diagnoses within 24-hours of discharge. Analysis was based on intention to treat. Results: We analyzed 225 participants (112 acetaminophen; 113 HBB). The mean (SD) age was 12.4 (3.0) years and 148/225 (65.8%) were females. Prior to enrollment, the median (IQR) duration of pain prior was 2 (4.5) hours and analgesia was provided to 101/225 (44.9%) of participants. The mean (SD) pre-intervention pain scores in the acetaminophen and HBB groups were 62.7 (15.9) mm and 60.3 (17.3) mm, respectively. At 80 minutes, the mean (SD) pain scores in the acetaminophen and HBB groups were 30.1 (28.8) mm and 29.4 (26.4) mm, respectively and there were no significant differences adjusting for pre-intervention scores (p = 0.96). The median (IQR) caregiver satisfaction was high in the acetaminophen [5 (2)] and HBB [5 (1)] groups (p = 0.79). The median (IQR) length of stay between acetaminophen [235 (101)] and HBB [234 (103)] was not significantly different (p = 0.53). The proportion of participants with a return visit for abdominal pain was 4/112 (3.5%) in the acetaminophen group and 6/113 (5.3%) in the HBB group. The most common adverse effect was nausea (9% in each group) and there were no significant differences in adverse effects between acetaminophen (26/112, 23.2%) and HBB (31/113, 27.4%) (p = 0.52). There were no missed surgical diagnoses. Conclusion: For children with presumed functional abdominal pain who present to the ED, both acetaminophen and HBB produce a clinically important (VAS < 30 mm) reduction in pain and should be routinely considered in this clinical setting.
The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.
Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.
One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.
A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.
Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
This article describes the design and implementation of a redistricting simulation in two classes at a large university. Simulations often include a high degree of abstraction and, as a result, may not inform and develop an understanding of how the world operates. We developed a binding-arbitration game, based on the New Jersey model of a bipartisan commission, in which groups of students used US Census data and a set of mandatory and discretionary criteria to design congressional districts in Louisiana as well as advocate for their plan at an open hearing. In so doing, they learned about the complexities of redistricting and were introduced to geographical information systems (GIS). The student-drawn maps, on average, were more compact and preserved a larger proportion of places and parishes in a single district than the legislature-drawn map. The article discusses other features of the students’ maps and concludes with comments on the general decision-game design.
Outpatient central venous catheters (CVCs) are being used more frequently; however, data describing mechanical complications and central-line–associated bloodstream infections (CLABSI) in the outpatient setting are limited. We performed a retrospective observational cohort study to understand the burden of these complications to elucidate their impact on the healthcare system.
Data were retrospectively collected on patients discharged from Vanderbilt University Medical Center with a CVC in place and admitted into the care of Vanderbilt Home Care Services. Risk factors for medically attended catheter-associated complications (CACs) and outpatient CLABSIs were analyzed.
A CAC developed in 143 patients (21.9%), for a total of 165 discrete CAC events. Among these, 76 (46%) required at least 1 visit to the emergency department or an inpatient admission, while the remaining 89 (54%) required an outpatient clinic visit. The risk for developing a CAC was significantly increased in female patients, patients with a CVC with >1 lumen, and patients receiving total parenteral nutrition. The absolute number of CLABSIs identified in the study population was small at 16, or 2.4% of the total cohort.
Medically attended catheter complications were common among outpatients discharged with a CVC, and reduction of these events should be the focus of outpatient quality improvement programs.
In Ramsey theory one wishes to know how large a collection of objects can be while avoiding a particular substructure. A problem of recent interest has been to study how large subsets of the natural numbers can be while avoiding three-term geometric progressions. Building on recent progress on this problem, we consider the analogous problem over quadratic number fields. We first construct high-density subsets of the algebraic integers of an imaginary quadratic number field that avoid three-term geometric progressions. When unique factorization fails, or over a real quadratic number field, we instead look at subsets of ideals of the ring of integers. Our approach here is to construct sets ‘greedily’, a generalization of the greedy set of rational integers considered by Rankin. We then describe the densities of these sets in terms of values of the Dedekind zeta function. Next, we consider geometric-progression-free sets with large upper density. We generalize an argument by Riddell to obtain upper bounds for the upper density of geometric-progression-free subsets, and construct sets avoiding geometric progressions with high upper density to obtain lower bounds for the supremum of the upper density of all such subsets. Both arguments depend critically on the elements with small norm in the ring of integers.
We examined two potentially interacting, connected pathways by which parental supportiveness during early adolescence (ages 1–13) may come to be associated with later African American young adult smoking. The first pathway is between parental supportiveness and young adult stress (age 19), with stress, in turn, predicting increased smoking at age 20. The second pathway is between supportive parenting and tumor necrosis factor (TNF) gene methylation (i.e., TNFm), a proinflammatory epitype, with low levels indicating greater inflammatory potential and forecasting increased risk for smoking in response to young adult stress. In a sample of 382 African American youth residing in rural Georgia, followed from early adolescence (age 10–11) to young adulthood (age 20), supportive parenting indirectly predicted smoking via associations with young adult stress, IE = –0.071, 95% confidence interval [–0.132, –0.010]. In addition, supportive parenting was associated with TNFm measured at age 20 (r = .177, p = .001). Further, lower TNFm was associated with a significantly steeper slope (b = 0.583, p = .003) of increased smoking in response to young adult stress compared to those with higher TNFm (b = 0.155, p = .291), indicating an indirect, amplifying role for supportive parenting via TNFm. The results suggest that supportive parenting in early adolescence may play a role in understanding the emergence of smoking in young adulthood.
Nursing home residents are at risk for acquiring and transmitting MDROs. A serial point-prevalence study of 605 residents in 3 facilities using random sampling found MDRO colonization in 45% of residents: methicillin-resistant Staphylococcus aureus (MRSA, 26%); extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL, 17%); vancomycin-resistant Enterococcus spp. (VRE, 16%); carbapenem-resistant Enterobacteriaceae (CRE, 1%). MDRO colonization was associated with history of MDRO, care needs, incontinence, and catheters.
With the Lick Observatory 3m telescope and image dissector scanner we have obtained new spectrophotometric observations of three halo planetary nebulae; 49 + 88°1, 108 − 76°1, and K 648. Based on the observed line intensities we are able to compute temperatures, densities, and abundances of He, 0, N, and Ne. Our data show that the helium abundance in the halo planetaries is normal with respect to disk planetaries. Oxygen is consistently less abundant in the halo planetaries by factors of 4, 12, and 20. The ratio N/0 in 49 + 88°1 and K 648 is typical of disk planetaries while N/0 in 108 − 76°1 is an order of magnitude larger. This suggests to us the possibility that varying amounts of mixing of CNO processed material has taken place in the progenitor stars. We do not detect [S II] or [S III] emission in K 648 or 108 − 76°1. In 49 + 88°1 [S II] and [S III] are present but weak and we derive an S abundance which is roughly a factor of 10 smaller than for disk planetaries. K 648 has the lowest abundances of 0, N, and Ne of all these halo planetary nebulae.
Papunya Tula Artists is a company owned and directed by Aboriginal people from the Western Desert, predominantly from the Luritja and Pintupi language groups. It currently has 49 shareholders and represents around 120 artists. The broad aims of the company are to promote individual artists, and to provide economic development for the communities to which they belong, thereby preserving and extending their traditional culture. Towards the end of 1993 the Art Gallery of New South Wales entered into a formal partnership with the company to assist it in preserving, copying and providing access to their immensely important archival records. The project, which at first seemed straightforward and easily manageable, raised a number of important issues about the provision of archival services for Indigenous art and provides a useful case study for reflecting on these.
Italy is celebrated for its outstanding patrimony in art and architecture. Less known are its equally rich libraries and archives. English researchers are sometimes daunted by the perceived barriers of language, cataloguing and access when they contemplate exploring these collections, scattered throughout the country in state, academic and ecclesiastical institutions. Steven Miller, acting Head Librarian of Sydney’s Art Gallery of New South Wales, shares his experience of using a wide range of Italian libraries and archives over the last ten years.
Molecular bands have been used as a diagnostic of spectral type since the 1860's. TiO was first identified as the dominant feature in optical spectra of cool giants in 1904 (Fowler 1904). Many diatomic molecules have now been included (e.g. Jørgensen & Larsson 1990) in detailed calculations of stellar opacity and attention is starting to focus on the incorporation of accurate data for triatomics. Triatomic molecules have a much greater density of states than diatomics; bending vibrational bands - generally lower in frequency than bond-stretching modes - may contribute considerably to “filling in” spectral gaps.
We use the underlying data of the IMPLAN Pro 3.0 regional economic simulation model to estimate the current economic contribution of Michigan's local food system and explore the chain of transactions giving rise to consumption of locally sourced goods from producer to processor to consumption. The proposed methodology includes both unprocessed and processed foods in the estimation of the local food system's economic value. The model also provides a replicable and consistent approach to estimating the value of local food systems within regional and state economies.
It is generally assumed that quasi-stellar objects represent phenomena taking place in galaxies. There are at least three lines of reasoning that lead to this viewpoint. First, there appears to be a continuity of properties extending from Seyfert galaxies and N systems to QSOs with the differences between the various groups principally a question of the contrast between the luminous central object and its surrounding galaxy. Since Seyfert galaxies and N systems are definitely in galaxies, it is concluded that QSOs must also be in galaxies which are not directly visible because of the high luminosity of the central object. A second argument is based on the result that QSOs do not appear to differ dramatically in abundances of elements from those which are typical of normal galaxies. With the prevailing view that virtually all the elements heavier than helium originated as a result of stellar processes, it would be concluded that QSOs must be associated with galaxies of stars that produced the heavier elements. A third, rather indirect argument is based on the results of Stockton (see his paper in this volume) and others that QSOs are often found in groups of galaxies and therefore are likely to be located in galaxies themselves (guilt by association). But the fact is that direct evidence that QSOs are in galaxies is sadly lacking.