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We analyzed antibiotic use data from 29 southeastern US hospitals over a 5-year period to determine changes in antibiotic use after the fluoroquinolone US Food and Drug Administration (FDA) advisory update in 2016. Fluoroquinolone use declined both before and after the FDA announcement, and the use of select, alternative antibiotics increased after the announcement.
Fluoroquinolones are among the 4 most commonly prescribed antibiotic classes.1,2 Postmarketing reports of serious adverse events linked to fluoroquinolones include tendonitis, neuropathy, hypoglycemia, psychiatric side effects, and possible aortic vessel rupture, leading to safety label changes in July 2008 and August 2013.3 In July 2016, the US Food and Drug Administration (FDA) strengthened the “black box” warning following an initial safety announcement in May 2016, recommending avoidance of fluoroquinolones for uncomplicated infections such as acute exacerbation of chronic bronchitis, uncomplicated urinary tract infections, and acute bacterial sinusitis.4 Concerns over safety and the association with Clostridiodes difficile infection have led inpatient antimicrobial stewardship programs (ASPs) to develop initiatives to promote avoidance of quinolones. The objective of this study was to quantify the effect of the 2016 FDA “black box” update on inpatient antibiotic use among a cohort of southeastern US hospitals.
To determine the feasibility and value of developing a regional antibiogram for community hospitals.
Multicenter retrospective analysis of antibiograms.
SETTING AND PARTICIPANTS
A total of 20 community hospitals in central and eastern North Carolina and south central Virginia participated in this study.
We combined antibiogram data from participating hospitals for 13 clinically relevant gram-negative pathogen–antibiotic combinations. From this combined antibiogram, we developed a regional antibiogram based on the mean susceptibilities of the combined data.
We combined a total of 69,778 bacterial isolates across 13 clinically relevant gram-negative pathogen–antibiotic combinations (median for each combination, 1100; range, 174–27,428). Across all pathogen–antibiotic combinations, 69% of local susceptibility rates fell within 1 SD of the regional mean susceptibility rate, and 97% of local susceptibilities fell within 2 SD of the regional mean susceptibility rate. No individual hospital had >1 pathogen–antibiotic combination with a local susceptibility rate >2 SD of the regional mean susceptibility rate. All hospitals’ local susceptibility rates were within 2 SD of the regional mean susceptibility rate for low-prevalence pathogens (<500 isolates cumulative for the region).
Small community hospitals frequently cannot develop an accurate antibiogram due to a paucity of local data. A regional antibiogram is likely to provide clinically useful information to community hospitals for low-prevalence pathogens.
For this study, we adapted the Montgomery Borgatta Caregiver Burden Scale, used widely in the United States, to the Saudi Arabian context. To produce an Arabic, culturally sensitive version of the scale, we conducted semi-structured interviews with 20 Saudi family caregivers. The Arabic version of the scale was tested, and participants were asked to comment on the appropriateness of items for the construct of “caregiver burden” using the repertory grid technique and laddering procedure – two constructivist methods derived from personal construct theory. From interview findings, we examined the content of the items and the caregiver burden construct itself. Our findings suggest that the use of constructivist methods to refine constructs and quantitative instruments is highly informative. This strategy is feasible even when little is known about the investigated constructs in the target culture and further elucidates our understanding of cross-cultural variations or invariance of different versions of the scale.
To estimate the proportion of products meeting Indian government labelling regulations and to examine the Na levels in packaged foods sold in India.
Nutritional composition data were collected from the labels of all packaged food products sold at Indian supermarkets in between 2012 and 2014. Proportions of products compliant with the Food Safety Standards Authority of India (FSSAI) regulations and labelled with Na content, and mean Na levels were calculated. Comparisons were made against 2010 data from Hyderabad and against the UK Department of Health (DoH) 2017 Na targets.
Eleven large chain retail stores in Delhi and Hyderabad, India.
Packaged food products (n 5686) categorised into fourteen food groups, thirty-three food categories and ninety sub-categories.
More packaged food products (43 v. 34 %; P<0·001) were compliant with FSSAI regulations but less (32 v. 38 %; P<0·001) reported Na values compared with 2010. Food groups with the highest Na content were sauces and spreads (2217 mg/100 g) and convenience foods (1344 mg/100 g). Mean Na content in 2014 was higher in four food groups compared with 2010 and lower in none (P<0·05). Only 27 % of foods in sub-categories for which there are UK DoH benchmarks had Na levels below the targets.
Compliance with nutrient labelling in India is improving but remains low. Many packaged food products have high levels of Na and there is no evidence that Indian packaged foods are becoming less salty.
A wide range of Arthurian material is discussed here, reflecting its diversity, and enduring vitality. Geoffrey of Monmouth's best-selling Historia regum Britannie is discussed in the context of Geoffrey's reception in Wales and the relationship between Latin and Welsh literary culture. Two essays deal with the Middle English Ywain and Gawain: the first offers a comparative study of the Middle English poem alongside Chrétien's Yvain and the Welsh Owein, while the second considers Ywain and Gawain with the Alliterative Morte Arthure in their northern English cultural and political context, the world of the Percys and the Nevilles. It is followed by a discussion of Edward III's recuperation of his abandoned Order of the Round Table, which offers an intriguing explanation for this reversal in the context of Edward's victory over the French at Poitiers. The final essay is a comparison of fifteenth- and twentieth-century portrayals of Camelot in Malory and T.H. White, as both idea and locale, and a centre of hearsay and gossip. The volume is completed with a unique and little-known medieval Greek Arthurian poem, presented in facing-page edition and modern English translation.
Elizabeth Archibald is Professor of English Studies at Durham University, and Principal of St Cuthbert's Society; David F. Johnson is Professor of English at Florida State University, Tallahassee.
Contributors: Christopher Berard, Louis J. Boyle, Thomas H. Crofts, Ralph Hanna, Georgia Lynn Henley, Erich Poppe
This volume of Arthurian Literature ranges from the reception of Geoffrey of Monmouth in Wales to the Camelot of T. H. White. Georgia Henley discusses Latin literary culture in medieval Wales, evaluating the intellectual and literary context in which Geoffrey of Monmouth's seminal Historia regum Britanniae was received. She makes the case for discarding the binary distinction of ‘Welsh vs Latin’ in favour of a view of medieval Wales as a multilingual culture in which Latin and Welsh existed side-by-side and the classical tradition had a significant influence on Welsh literature.
We are pleased to be able to publish a revised version of Prof. Erich Poppe's 2016 O'Donnell Lecture in Celtic Studies, in which he shines a bright comparative light (in terms of both plot and lexis) on Chrétien's Ivain, the Middle English Ywain and Gawain and the Middle Welsh Owein, otherwise known as Chwedyl Iarlles y Ffynnawn (The Tale of the Lady of the Well / Countess of the Spring). In his reading of these poems, Poppe effectively demonstrates Peter Clemoes’ axiom that to read ‘Medieval Welsh literature alongside that of Middle English’ is to recognize how great a debt English literature owes to the Celtic tradition for its Arthurian inspirations.
Christopher Berard returns to the subject of Edward III's abandoned Order of the Round Table to argue that, while Edward's ‘un-Arthurian’ tactics at Crécy made his association with the legendary king problematic, his victory at Poitiers and the capture of the flower of French knighthood – and of Jean II of France himself – rendered that association apt once more. Portraying himself as an Arthurian ‘King of Kings’ enabled Edward to negotiate a treaty with, and seek ransom for, the French king without undermining his own claim to that throne.
Ralph Hanna considers Ywain and Gawain and the Alliterative Morte Arthure in the cultural and political context of the turbulent history of the borders and of two great northern families, the Percys and the Nevilles. In spite of the popular image of the ‘uncouth / violent North’, he argues that northern romances diverge from the popular insular pattern of usurpation, exile and return, focusing instead on more domestic themes and on ‘the failure of mere martial prowess to offer meaningful achievement’. He sees Ywain and Gawain as a response to criticism of romance in texts such as Cursor mundi, stressing the importance of both time and ‘trowth’.
Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures of parenting, and parent interviews for anxiety disorder history, and children were genotyped for the 5-HTTLPR. Parent factors did not moderate the association between age 3 and age 5 BI; however, child BI at age 3 interacted with children's 5-HTTLPR variants to predict age 5 BI, such that children with at least one copy of the short allele exhibited less continuity of BI over time relative to children without this putative plasticity variant. Findings are consistent with previous work indicating the 5-HTTLPR short variant increases plasticity to contextual influences, thereby serving to decrease the continuity of BI in early childhood.
α-Tocopherol is the principal source of vitamin E, an essential nutrient that plays a crucial role in maintaining healthy brain function. Infant formula is routinely supplemented with synthetic α-tocopherol, a racaemic mixture of eight stereoisomers with less bioactivity than the natural stereoisomer RRR-α-tocopherol. α-Tocopherol stereoisomer profiles have not been previously reported in the human brain. In the present study, we analysed total α-tocopherol and α-tocopherol stereoisomers in the frontal cortex (FC), hippocampus (HPC) and visual cortex (VC) of infants (n 36) who died of sudden infant death syndrome or other conditions. RRR-α-tocopherol was the predominant stereoisomer in all brain regions (P<0·0001) and samples, despite a large intra-decedent range in total α-tocopherol (5–17 μg/g). Mean RRR-α-tocopherol concentrations in FC, HPC and VC were 10·5, 6·8 and 5·5 μg/g, respectively. In contrast, mean levels of the synthetic stereoisomers were RRS, 1–1·5; RSR, 0·8–1·0; RSS, 0·7–0·9; and Σ2S 0·2–0·3 μg/g. Samples from all but two decedents contained measurable levels of the synthetic stereoisomers, but the intra-decedent variation was large. The ratio of RRR:the sum of the synthetic 2R stereoisomers (RRS+RSR+RSS) averaged 2·5, 2·3 and 2·4 in FC, HPC and VC, respectively, and ranged from 1 to at least 4·7, indicating that infant brain discriminates against synthetic 2R stereoisomers in favour of RRR. These findings reveal that RRR-α-tocopherol is the predominant stereoisomer in infant brain. These data also indicate that the infant brain discriminates against the synthetic 2R stereoisomers, but is unable to do so completely. On the basis of these findings, investigation into the impact of α-tocopherol stereoisomers on neurodevelopment is warranted.
A recent editorial claimed that the 2014 National Institute for Health and Care Excellence (NICE) guideline on psychosis and schizophrenia, unlike its equivalent 2013 Scottish Intercollegiate Guidelines Network (SIGN) guideline, is biased towards psychosocial treatments and against drug treatments. In this paper we underline that the NICE and SIGN guidelines recommend similar interventions, but that the NICE guideline has more rigorous methodology. Our analysis suggests that the authors of the editorial appear to have succumbed to bias themselves.
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)
Serum and erythrocyte (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured the serum folate forms (5-methyltetrahydrofolate (5-methylTHF), unmetabolised folic acid (UMFA), non-methyl folate (sum of tetrahydrofolate (THF), 5-formyltetrahydrofolate (5-formylTHF), 5,10-methenyltetrahydrofolate (5,10-methenylTHF)) and MeFox (5-methylTHF oxidation product)) by HPLC–MS/MS and RBC total folate by microbiologic assay in US population ≥ 1 year (n approximately 7500) participating in the National Health and Nutrition Examination Survey 2011–2. Data analysis for serum total folate was conducted including and excluding MeFox. Concentrations (geometric mean; detection rate) of 5-methylTHF (37·5 nmol/l; 100 %), UMFA (1·21 nmol/l; 99·9 %), MeFox (1·53 nmol/l; 98·8 %), and THF (1·01 nmol/l; 85·2 %) were mostly detectable. 5-FormylTHF (3·6 %) and 5,10-methenylTHF (4·4 %) were rarely detected. The biggest contributor to serum total folate was 5-methylTHF (86·7 %); UMFA (4·0 %), non-methyl folate (4·7 %) and MeFox (4·5 %) contributed smaller amounts. Age was positively related to MeFox, but showed a U-shaped pattern for other folates. We generally noted sex and race/ethnic biomarker differences and weak (Spearman's r< 0·4) but significant (P< 0·05) correlations with physiological and lifestyle variables. Fasting, kidney function, smoking and alcohol intake showed negative associations. BMI and body surface area showed positive associations with MeFox but negative associations with other folates. All biomarkers showed significantly higher concentrations with recent folic acid-containing dietary supplement use. These first-time population data for serum folate forms generally show similar associations with demographic, physiological and lifestyle variables as serum total folate. Patterns observed for MeFox may suggest altered folate metabolism dependent on biological characteristics.
Effectiveness studies of preschool social–emotional programs are needed in low-income, diverse populations to help promote the well-being of at-risk children. Following an initial program efficacy study 2 years prior, 248 culturally diverse Head Start preschool children participated in the current effectiveness trial and received either the Emotion-Based Prevention Program (EBP) or the I Can Problem Solve (ICPS) intervention. Pre- and postdata collection included direct child assessment, teacher report, parent interview, and independent observations. Teachers implementing the EBP intervention demonstrated good and consistent fidelity to the program. Overall, children in EBP classrooms gained more emotion knowledge and displayed greater decreases in negative emotion expressions and internalizing behaviors across the implementation period as compared to children in ICPS classrooms. In addition, cumulative risk, parental depressive symptoms, and classroom climate significantly moderated treatment effects. For children experiencing more stress or less support, EBP produced more successful outcomes than did ICPS. These results provide evidence of EBP sustainability and program effectiveness, as did previous findings that demonstrated EBP improvements in emotion knowledge, regulation skills, and behavior problems replicated under unsupervised program conditions.