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A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.
Y.Ba2Cu3O7, a high TC superconductor powder, was shock compacted and explosively welded inside a copper matrix using the explosive fabrication methods described by Murr, Hare and Eror. The shock compression fabrication technique provides the ability to process the superconductor powders into useable structures that will minimize environmental degradation and will not negatively affect the physical or mechanical properties. Additionally, the introduction of shock induced defects are known to increase solid-state reactivity in ceramic materials. For this reason, shock compression fabrication of the superconductor/copper system offers the possibility of enhancing the superconducting properties of the YBa2Cu3O7 powders.
Many countries have a national antimicrobial resistance strategy. In Australia, primary care is especially important because this setting encompasses a high proportion of antibiotic use. While antibiotic use decreased during the 1990s, it began to increase again in the mid-2000s. In response to this, in 2009 NPS MedicineWise implemented a series of nationwide educational interventions for consumers, family physicians (general practitioners), and community pharmacies that aimed to reduce excessive antibiotic use.
For consumers a social marketing approach was used, including strategies that leveraged collectivism, nudge theory, celebrity endorsement, and co-creation. Channels included social, print, radio, and other media as well as practice waiting rooms and pharmacies. For health professionals, interventions included face-to-face education, audits, comparative prescribing feedback, case studies, and point-of-care materials. Surveys of consumers and family physicians were conducted periodically to evaluate changes in knowledge and behavior. National Pharmaceutical Benefits Scheme claims data were analyzed using a Bayesian structural time-series model to estimate the cumulative effect of interventions by comparing the observed and expected monthly dispensing volumes if the interventions had not occurred.
The consumer survey results indicated that more people were aware of antibiotic resistance (seventy-four percent in 2017 versus seventy percent in 2014), with the minority requesting or expecting antibiotics for upper respiratory tract infections (URTIs) (twenty-two percent in 2017). People underestimated the usual duration of symptoms for URTIs and were more inclined to expect antibiotics beyond that timeframe. Compared with non-participants, family physicians who participated in the program reported more frequent discussions about hand hygiene (ninety percent versus eighty-two percent) and proper use of antibiotics with patients (ninety-five percent versus eighty-eight percent). Between 2009 and 2015 there was an estimated fourteen percent reduction in prescriptions dispensed to concessional patients for antibiotics commonly prescribed for URTIs.
Family physicians and consumers have responded positively to national programs. Sustaining and building on these improvements will require continued education and further innovation.
The purpose of this study was to determine the effect of a whole-food protein (cottage cheese, CC) consumed before sleep on next-morning resting energy expenditure (REE), RER and appetite compared with an isoenergetic/isonitrogenous casein protein (CP) supplement and placebo (PL) in active women. In a beverage-blinded, randomised, cross-over design, ten active women (age, 23·1 (sd 1·9) years; body fat, 22·0 (sd 4·6) %) consumed pre-sleep CC (30 g of protein, 10 g of carbohydrate and 0 g of fat) or energy- and protein-matched liquid CP or PL (0 kJ). Participants arrived at 18.00 hours for an overnight stay in the laboratory. At 30–60 min before normal bed time (2 h post standard meal), participants consumed CC, CP or PL before measurement of REE. Upon waking (05.00–08.00 hours), REE was repeated and subjective appetite was recorded. Statistical analyses were conducted using repeated-measures ANOVA (SPSS). Significance was accepted at P≤0·05. There were no significant differences in acute REE (CC, 7217 (sd 1368); CP, 7188 (SD 895); PL, 7075 (sd 1108) kJ/d, P=0·95), acute RER (0·79 (sd 0·05), P=0·56), morning REE (CC, 5840 (sd 1225); CP, 5694 (sd 732); PL, 5991 (sd 903) kJ/d, P=0·79) or morning RER (0·77 (sd 0·03), P=0·52). Subjective measures of appetite were not different between groups. In active women, pre-sleep consumption of CC does not alter REE or RER more than a CP or PL beverage. These data suggest that the metabolic response from whole-food protein do not differ from the metabolic response of liquid protein.
Glioblastoma is the most common and malignant brain tumor with a median overall survival of 20.5 months. There is an urgent need to develop novel therapeutic strategies. Using a glioblastoma TCGA dataset, we have determined that high NSUN5 mRNA expression is strongly associated with poor survival in glioblastoma patients. NSUN5 is a ribosomal RNA (rRNA) cytosine methyltransferase. Human NSUN5 is located in chromosome 7 and is completely deleted in the Williams-Beurren syndrome, a complex neurodevelopmental disorder. However, RNA targets of NSUN5 in mammals and its role in cancer are unknown. The objective of this project is to determine whether elevated NSUN5 changes rRNA methylation pattern and thereby leads to pro-tumorigenic translational reprogramming and pro-tumorigenic phenotypes in glioblastoma. Western blotting showed that NSUN5 is expressed in 7 out of 9 established glioblastoma cell lines and in 8 out of 12 primary patient-derived glioblastoma cell lines. Bisulfite sequencing confirmed that NSUN5 methylates C3782 of human 28S rRNA in glioblastoma cells. Functionally, overexpression of NSUN5 increases, whereas NSUN5 knockout decreases global protein synthesis and sphere formation in glioblastoma cells. More importantly, mice bearing intracranial NSUN5-expressing U87 tumors survived for a shorter time than mice bearing tumors derived from U87 control cells. Our results suggest that NSUN5 methylates 28S rRNA and may enhance cancer stem cell phenotypes and tumor formation and/or progression in glioblastoma. Experiments are ongoing to determine whether NSUN5 promotes tumor formation and/or progression through translational reprogramming in glioblastoma. This study may help identify novel therapeutic targets for glioblastoma.
Parenting, Eating and Activity for Child Health (PEACH) is a multi-component lifestyle intervention for families with overweight and obese children. PEACH was translated from an efficacious randomised-controlled trial (RCT) and delivered at scale as PEACH Queensland (QLD) in Queensland, Australia. The aim of this study is to explore pre–post changes in parenting, and child-level eating, activity and anthropometry, in the PEACH QLD service delivery project. PEACH QLD enrolled 926 overweight/obese children (817 families). Pre-programme evaluation was completed for 752 children and paired pre–post-programme evaluation data were available for 388 children. At baseline, children with pre–post-programme data were (mean) 8·8 years old, and at follow-up were 9·3 years old, with mean time between pre–post-programme measures of 0·46 years. Outcomes reflected each domain of the PEACH programme: parenting, eating behaviour of the child and activity behaviours (means reported). Parents reported improvements in parenting self-efficacy (3·6 to 3·7, P=0·001). Children had improved eating behaviours: eating more daily serves of vegetables (2·0 to 2·6, P=0·001) and fewer non-milk sweetened beverages (0·9 to 0·6, P=0·001) and discretionary foods (2·2 to 1·5, P=0·001). Children spent more time in moderate-to-vigorous physical activity (86 to 105 min/d, P=0·001) and less time in sedentary screen-based behaviours (190 to 148 min/d, P=0·001). Consequently, there were significant improvements in mean BMIz (−0·112; P<0·001) and weight status (healthy weight/overweight/obese/morbidly obese prevalence from 0/22/33/45 % to 2/27/34/37 %, P<0·001). When delivered at scale, PEACH remains an effective family-based, multi-component, lifestyle weight management programme for overweight and obese children whose families engage in the programme.
OBJECTIVES/SPECIFIC AIMS: Peripheral neuropathy is the dose limiting toxicity of paclitaxel treatment. Paclitaxel pharmacokinetics (PK), specifically the Cmax and amount of time the concentration remains above 0.05 µM (Tc>0.05), have been associated with occurrence of severe, clinician-documented neuropathy. The objective of this study was to confirm that paclitaxel PK predicts progression of patient-reported neuropathy. METHODS/STUDY POPULATION: This observational trial enrolled breast cancer patients receiving weekly 1-hour paclitaxel infusions (80 mg/m2×12 cycles) at the University of Michigan Comprehensive Cancer Center. Paclitaxel concentration was measured via LC/MS in plasma samples collected at the end of (Cmax) and 16–24 hours after (Tc>0.05) first infusion. Patient-reported neuropathy was collected (EORTC CIPN20) at baseline and each cycle. The rate of neuropathy severity increase per treatment cycle is being modeled for each patient. Cmax and Tc>0.05 values will be introduced into the model to confirm that PK independently contributes to neuropathy progression. RESULTS/ANTICIPATED RESULTS: PK and neuropathy data have been collected from 60 patients for ongoing analysis. Our initial model will characterize the expected severity of neuropathy after each cycle of paclitaxel treatment. The PK-neuropathy model will include either PK parameter to validate their contribution to the progression of neuropathy severity during treatment. We anticipate, based on our preliminary analysis of the first 16 patients, that both PK parameters will significantly contribute to the model but Tc>0.05 will be more strongly associated with neuropathy progression. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will generate a model that can be used to predict a patient’s neuropathy severity throughout treatment using a single, conveniently collected and easily measured PK sample during their first cycle. The next steps of this project include identifying genetic and metabolomic biomarkers that predict which patients experienced more severe neuropathy than would be anticipated based on their paclitaxel PK, and a planned interventional trial of personalized paclitaxel dosing to enhance efficacy and/or prevent neuropathy.
We examined the impact of methicillin-resistant Staphylococcus aureus (MRSA) guidelines in Québec adult hospitals from January 1, 2006, to March 31, 2015, by examining the incidence rate reduction (IRR) in healthcare-associated MRSA bloodstream infections (HA-MRSA), using central-line associated bloodstream infections (CLABSIs) as a comparator.
In this study, we utilized a quasi-experimental design with Poisson segmented regression to model HA-MRSA and CLABSI incidence for successive 4-week surveillance segments, stratified by teaching status. We used 3 distinct periods with 2 break points (April 1, 2007, and January 3, 2010) corresponding to major MRSA guideline publications and updates.
Over the study period, HA-MRSA incidence decreased significantly in adult teaching facilities but not in nonteaching facilities. Prior to MRSA guideline publication (2006–2007), HA-MRSA incidence decrease was not significant (P=.89), while CLABSI incidence decreased by 4% per 4-week period (P=.05). After the publication of guidelines (2007–2009), HA-MRSA incidence decreased significantly by 1% (P=.04), while no significant decrease in CLABSI incidence was observed (P=.75). HA-MRSA and CLABSI decreases were both significant at 1% for 2010–2015 (P<.001 and P=.01, respectively). These decreases were gradual rather than sudden; break points were not significant. Teaching facilities drove these decreases.
During the study period, HA-MRSA and CLABSI rates decreased significantly. In 2007–2009, the significant decrease in HA-MRSA rates with stable CLABSI rates suggests an impact from MRSA-specific guidelines. In 2010–2015, significant and equal IRRs for HA-MRSA and CLABSI may be due to the continuing impact of MRSA guidelines, to the impact of new interventions targeting device-associated infections in general by the 2010–2015 Action Plan, or to a combination of factors.
Objectives: The Quebec Trauma Care Continuum (TCC) was initiated in 1991 with the objective of providing accessible, continuous, efficient, and high quality services for all injury cases in the province.
Methods: The TCC design relied on three key components: (i) the designation of a network of acute care and rehabilitation facilities with specific mandates and responsibilities; (ii) the elaboration of transfer protocols, standing agreements, and governing structures to ensure fluid and optimal patient flow; and (iii) the close monitoring of several indicators to facilitate the continuous evaluation and improvement of the network.
Results: Between 1992 and 2002, in-hospital mortality following major trauma decreased from 51.8 percent to 8.6 percent, followed by an additional 24 percent drop between 1999 and 2012. We also observed a 16 percent decrease in average LOS but no change in the incidence of complications or unplanned readmissions. These changes translate into 186 lives saved per year and cost savings, due to shorter LOS, of 6.3 million CD$ per year. The risk-adjusted incidence of in-hospital mortality following major injury between 2006 and 2012 (7 percent) was the lowest of all Canadian provinces.
Conclusions: Strategic transformation of a network's structure and processes, supported by continuous monitoring of validated quality indicators, can lead to significant and sustainable improvements in clinical outcomes. It is hoped that the Quebec trauma story will inspire other jurisdictions and other healthcare sectors.
This volume explores the diverse ways in which the Book of Psalms profoundly influenced medieval English literature and culture, through a series of connected overviews and special case studies. A number of recent studies have highlighted the Psalter's reception in Early Modern English (and wider European culture), while three monographs by contributors to this volume offer focused studies of the Psalter in individual periods of medieval English literature: Jane Toswell's The Anglo-Saxon Psalter, Annie Sutherland's English Psalms in the Middle Ages: 1300–1450and Michael P. Kuczynski's Prophetic Song: The Psalms as Moral Discourse in Late Medieval England. But as yet no single study has sought to offer a comprehensive survey of English responses to the Book of Psalms from the conversion of the Anglo-Saxons to the cusp of the Reformation. By bringing work by experts on both Old and Middle English literature into dialogue, this volume breaks down the traditional disciplinary binaries of pre- and post-Conquest English, late medieval and Early Modern, as well as emphasizing the complex and fascinating relationship between Latin and the vernacular languages of England. In order to encourage the reader to make connections both across and within these various periods and languages, the book is arranged thematically rather than chronologically, with three sections designed to offer a variety of perspectives on the Psalms and medieval English literature.
Section I (Translation) focuses on the development of English psalm translation from its beginnings in Old English interlinear glosses in Latin psalters through the multilingual psalters of the Anglo-Norman era to the stand-alone vernacular psalters of the fourteenth and fifteenth centuries. Concentrating on the Psalter as a book, this section charts the emergence of English as a scriptural language in the medieval period.
Section II (Adaptation) considers how medieval English prose and verse writers draw on the Psalms as a source of literary inspiration. Demonstrating how the Psalter could be adapted and redeployed within the context of medieval worship and prayer, it begins with a discussion of the first adaptation of the entire Psalter into English verse, before turning to a consideration of the development of the abbreviated psalter tradition. This section also addresses the wider influence of psalmic language and imagery on Old English praise and lament poetry, and on Middle English alliterative verse.