To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
Improved plasticity models require simultaneous experimental local strain and microstructural evolution data. Microscopy tools, such as electron backscatter diffraction (EBSD), that can monitor transformation at the relevant length-scale, are often incompatible with digital image correlation (DIC) techniques required to determine local deformation. In this paper, the viability of forescatter detector (FSD) images as the basis for the DIC study is investigated. Standard FSD and an integrated EBSD/FSD approach (Pattern Region of Interest Analysis System: PRIAS™) are analyzed. Simultaneous strain and microstructure maps are obtained for tensile deformation of Q&P 1180 steel up to ~14% strain. Tests on an undeformed sample that is simply shifted indicate a standard deviation of error in strain of around 0.4% without additional complications from a deformed surface. The method resolves strain bands at ~2 μm spacing but does not provide significant sub-grain strain resolution. Similar resolution was obtained for mechanically polished and electropolished samples, despite electropolished surfaces presenting a smoother, simpler topography. While the resolution of the PRIAS approach depends upon the EBSD step size, the 80 nm step size used provides seemingly similar resolution as 8,000× (22.7 nm) FSD images. Surface feature evolution prevents DIC analysis across large strain steps (>6% strain), but restarting DIC, using an FSD reference image from an interim strain step, allows reasonable DIC across the stress–strain curve. Furthermore, the data are obtained easily and provide complementary information for EBSD analysis.
In 2018 Pearson et al. published a new sequence of annual radiocarbon (14C) data derived from oak (Quercus sp.) trees from Northern Ireland and bristlecone pine (Pinus longaeva) from North America across the period 1700–1500 BC. The study indicated that the more highly resolved shape of an annually based calibration dataset could improve the accuracy of 14C calibration during this period. This finding had implications for the controversial dating of the eruption of Thera in the Eastern Mediterranean. To test for interlaboratory variation and improve the robustness of the annual dataset for calibration purposes, we have generated a replicate sequence from the same Irish oaks at ETH Zürich. These data are compatible with the Irish oak 14C dataset previously produced at the University of Arizona and are used (along with additional data) to examine inter-tree and interlaboratory variation in multiyear annual 14C time-series. The results raise questions about regional 14C offsets at different scales and demonstrate the potential of annually resolved 14C for refining subdecadal and larger scale features for calibration, solar reconstruction, and multiproxy synchronization.
ALKS 3831, a combination of olanzapine and samidorphan (OLZ/SAM) in development for schizophrenia, is intended to mitigate olanzapine-associated weight gain. This thorough QT (tQT) study evaluated OLZ/SAM effects on electrocardiogram parameters.
In this randomized, double-blind, parallel-group study, 100 patients with stable schizophrenia were randomized 3:2 to either receive OLZ/SAM 10/10 mg (therapeutic dose) on days 2–4, 20/20 mg on days 5–8, and 30/30 mg (supratherapeutic dose) on days 9–13 with moxifloxacin-matching placebo on days 1 and 14, or a single dose of moxifloxacin 400 mg and matching placebo on days 1 and 14 (nested crossover design). Drug concentration relation to change from baseline in Fridericia-corrected QTc (ΔQTcF) was evaluated using a linear mixed-effect concentration-QTc (C-QTc) model. Adverse events were assessed.
The slope (90% CI) of the C-QTc was not significant for olanzapine or samidorphan (0.03 [−0.01, 0.08] and 0.01 [−0.01, 0.04] msec per ng/mL, respectively). Predicted placebo-corrected ΔQTcF (90% CI) was 2.33 (−2.72, 7.38) and 1.38 (−3.37, 6.12) msec at the observed geometric mean maximal concentration of olanzapine (62.6 ng/mL) and samidorphan (75.1 ng/mL), respectively, on day 13. A clinically relevant QT effect (ie, placebo-corrected ΔQTcF ≥10 msec) can be excluded for olanzapine and samidorphan concentrations up to ≈110 and ≈160 ng/mL, respectively. Assay sensitivity was confirmed by the C-QTc relationship of moxifloxacin. OLZ/SAM was well tolerated.
OLZ/SAM, in doses and plasma concentrations up to supratherapeutic levels, was well tolerated and had no clinically relevant effects on electrocardiogram parameters, including QT interval, in patients with schizophrenia.
Landscapes are defined as ‘an area, as perceived by people, whose character is the result of the action and interaction of natural and/or human factors’ (Council of Europe, 2000). Cultural landscapes are defined by the UNESCO World Heritage Convention (1992) as distinct geographical areas or properties uniquely ‘represent[ing] the combined work of nature and of man’. It also describes cultural landscapes as a ‘diversity of manifestations of the interaction between humankind and its natural environment’, and that the protection of traditional cultural landscapes can contribute to maintaining biological diversity. Indeed, Pilgrim and Pretty (2010) propose that the resilience of ecocultural systems is at its strongest when biological and cultural diversity can be considered as an interdependent whole.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Nutritional factors and infectious agents may contribute to paediatric growth deficits in low- and middle-income countries; however, the contribution of enteric pathogens is only beginning to be understood. We analysed the stool from children <5 years old from an open cohort, cluster-randomised controlled trial of a point-of-collection water chlorinator in urban Bangladesh. We compared the presence/absence of 15 enteric pathogens detected via multiplex, molecular methods in the stool with concurrent Z-scores/Z-score cut-offs (−2 standard deviations (s.d.)) for height-for-age (HAZ/stunting), weight-for-age (WAZ/underweight) and weight-for-height (WHZ/wasting), adjusted for sociodemographic and trial-related factors, and measured caregiver-reported diarrhoea. Enteric pathogen prevalence in the stool was high (88% had ≥1 enteric pathogen, most commonly Giardia spp. (40%), Salmonella enterica (33%), enterotoxigenic E. coli (28%) and Shigella spp. (27%)) while reported 7-day diarrhoea prevalence was 6%, suggesting high subclinical infection rates. Many children were stunted (26%) or underweight (24%). Adjusted models suggested Giardia spp. detection was associated with lower HAZ (−0.22 s.d., 95% CI −0.44 to 0.00; prevalence ratio for stunting: 1.39, 95% CI 0.94–2.06) and potentially lower WAZ. No pathogens were associated with reported diarrhoea in adjusted models. Giardia spp. carriage may be associated with growth faltering, but not diarrhoea, in this and similar low-income settings. Stool-based enteric pathogen detection provides a direct indication of previous exposure that may be useful as a broader endpoint of trials of environmental interventions.
This is a cross-sectional study aiming to understand the early characteristics and background of bone health impairment in clinically well children with Fontan circulation.
We enrolled 10 clinically well children with Fontan palliation (operated >5 years before study entrance, Tanner stage ≤3, age 12.1 ± 1.77 years, 7 males) and 11 healthy controls (age 12.0 ± 1.45 years, 9 males) at two children’s hospitals. All patients underwent peripheral quantitative CT. For the Fontan group, we obtained clinical characteristics, NYHA class, cardiac index by MRI, dual x-ray absorptiometry, and biochemical studies. Linear regression was used to compare radius and tibia peripheral quantitative CT measures between Fontan patients and controls.
All Fontan patients were clinically well (NYHA class 1 or 2, cardiac index 4.85 ± 1.51 L/min/m2) and without significant comorbidities. Adjusted trabecular bone mineral density, cortical thickness, and bone strength index at the radius were significantly decreased in Fontan patients compared to controls with mean differences −30.13 mg/cm3 (p = 0.041), −0.31 mm (p = 0.043), and −6.65 mg2/mm4 (p = 0.036), respectively. No differences were found for tibial measures. In Fontan patients, the mean height-adjusted lumbar bone mineral density and total body less head z scores were −0.46 ± 1.1 and −0.63 ± 1.1, respectively, which are below the average, but within normal range for age and sex.
In a clinically well Fontan cohort, we found significant bone deficits by peripheral quantitative CT in the radius but not the tibia, suggesting non-weight-bearing bones may be more vulnerable to the unique haemodynamics of the Fontan circulation.
Encephalitis causes high morbidity and mortality. An incidence of 4.3 cases of encephalitis/100 000 population has been reported in the UK. We performed a retrospective evaluation of the diagnosis and management of adults admitted to hospital with a clinical diagnosis of encephalitis/meningoencephalitis. Clinical, laboratory and radiological data were collated from electronic records. Thirty-six patients, median age 55 years and 24 (67%) male were included. The aetiology was confirmed over nine months in 25 (69%) of whom 16 were infections (six viral, seven bacterial, two parasitic and one viral and parasitic co-infection); 7 autoimmune; 1 metabolic and 1 neoplastic. Of 24 patients with fever, 15 (63%) had an infection. The median time to computed topography, magnetic resonance imaging and electroencephalography (EEG) was 1, 8 and 3 days respectively. Neuroimaging was abnormal in 25 (69%) and 17 (89%) had abnormal EEGs. Only 19 (53%) received aciclovir treatment. Six (17%) made good recoveries, 16 (44%) had moderate disability, 8 (22%) severe disability and 6 (17%) died. Outcomes were worse for those with an infectious cause. In summary, a diagnosis was made in 69.4% of patients admitted with encephalitis/meningoencephalitis. Autoimmune causes are important to consider at an early stage due to a successful response to treatment. Only 53% of patients received aciclovir on admission. Neuroimaging and EEG studies were delayed. The results of this work resulted in further developing the clinical algorithm for managing these patients.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to evaluate specific aspects of instrument performance of both X-ray and neutron powder diffractometers. This report describes SRM 660c, the fourth generation of this powder diffraction SRM, which is used primarily for calibrating powder diffractometers with respect to line position and line shape for the determination of the instrument profile function (IPF). It is certified with respect to lattice parameter and consists of approximately 6 g of lanthanum hexaboride (LaB6) powder. So that this SRM would be applicable for the neutron diffraction community, the powder was prepared from an isotopically enriched 11B precursor material. The microstructure of the LaB6 powder was engineered specifically to yield a crystallite size above that where size broadening is typically observed and to minimize the crystallographic defects that lead to strain broadening. A NIST-built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the LaB6 powder. Both Type A, statistical, and Type B, systematic, uncertainties have been assigned to yield a certified value for the lattice parameter at 22.5 °C of a = 0.415 682 6 ± 0.000 008 nm (95% confidence).
Research on psychotic illness is loosening emphasis on diagnostic stringency in favour of including a more dimensionally based conceptualization of psychopathology and pathobiology. However, to clarify these notions requires investigation of the full scope of psychotic diagnoses.
The Cavan–Monaghan First Episode Psychosis Study ascertained cases of first episode psychosis across all 12 DSM-IV psychotic diagnoses via all routes to care: public, private or forensic; home-based, outpatient or inpatient. There was no arbitrary upper age cut-off and minimal impact of factors associated with variations in social milieu, ethnicity or urbanicity. Cases were evaluated epidemiologically and assessed for psychopathology, neuropsychology, neurology, antecedent factors, insight and quality of life.
Among 432 cases, the annual incidence of any DSM-IV psychotic diagnosis was 34.1/100 000 of population and encompassed functional psychotic diagnoses, substance-induced psychopathology and psychopathology due to general medical conditions, through to psychotic illness that defied contemporary diagnostic algorithms. These 12 DSM-IV diagnostic categories, including psychotic disorder not otherwise specified, showed clinical profiles that were consistently more similar than distinct.
There are considerable similarities and overlaps across a broad range of diagnostic categories in the absence of robust discontinuities between them. Thus, psychotic illness may be of such continuity that it cannot be fully captured by operational diagnostic algorithms that, at least in part, assume discontinuities. This may reflect the impact of diverse factors each of which acts on one or more overlapping components of a common, dysfunctional neuronal network implicated in the pathobiology of psychotic illness.
Short-term survival after paediatric cardiac surgery has improved significantly over the past 20 years and increasing attention is being given to measuring and reducing incidence of morbidities following surgery. How to best use routinely collected data to share morbidity information constitutes a challenge for clinical teams interested in analysing their outcomes for quality improvement. We aimed to develop a tool facilitating this process in the context of monitoring morbidities following paediatric cardiac surgery, as part of a prospective multi-centre research study in the United Kingdom.
We developed a prototype software tool to analyse and present data about morbidities associated with cardiac surgery in children. We used an iterative process, involving engagement with potential users, tool design and implementation, and feedback collection. Graphical data displays were based on the use of icons and graphs designed in collaboration with clinicians.
Our tool enables automatic creation of graphical summaries, displayed as a Microsoft PowerPoint presentation, from a spreadsheet containing patient-level data about specified cardiac surgery morbidities. Data summaries include numbers/percentages of cases with morbidities reported, co-occurrences of different morbidities, and time series of each complication over a time window.
Our work was characterised by a very high level of interaction with potential users of the tool, enabling us to promptly account for feedback and suggestions from clinicians and data managers. The United Kingdom centres involved in the project received the tool positively, and several expressed their interest in using it as part of their routine practice.
The Green et al., Paranoid Thoughts Scale (GPTS) – comprising two 16-item scales assessing ideas of reference (Part A) and ideas of persecution (Part B) – was developed over a decade ago. Our aim was to conduct the first large-scale psychometric evaluation.
In total, 10 551 individuals provided GPTS data. Four hundred and twenty-two patients with psychosis and 805 non-clinical individuals completed GPTS Parts A and B. An additional 1743 patients with psychosis and 7581 non-clinical individuals completed GPTS Part B. Factor analysis, item response theory, and receiver operating characteristic analyses were conducted.
The original two-factor structure of the GPTS had an inadequate model fit: Part A did not form a unidimensional scale and multiple items were locally dependant. A Revised-GPTS (R-GPTS) was formed, comprising eight-item ideas of reference and 10-item ideas of persecution subscales, which had an excellent model fit. All items in the new Reference (a = 2.09–3.67) and Persecution (a = 2.37–4.38) scales were strongly discriminative of shifts in paranoia and had high reliability across the spectrum of severity (a > 0.90). The R-GPTS score ranges are: average (Reference: 0–9; Persecution: 0–4); elevated (Reference: 10–15; Persecution: 5–10); moderately severe (Reference: 16–20; Persecution:11–17); severe (Reference: 21–24; Persecution: 18–27); and very severe (Reference: 25+; Persecution: 28+). Recommended cut-offs on the persecution scale are 11 to discriminate clinical levels of persecutory ideation and 18 for a likely persecutory delusion.
The psychometric evaluation indicated a need to improve the GPTS. The R-GPTS is a more precise measure, has excellent psychometric properties, and is recommended for future studies of paranoia.
The third Viscount Palmerston (1784–1865) left his mark on the Victorian period as a prominent British statesman (notably his tenure of the Foreign Office, 1830–4, 1835–41 and 1846–51, the Home Office 1852–5, and his two terms as Prime Minister, 1855–8 and 1859–65). His frequently overlooked role as a landlord in Ireland, however, shows in important ways how his Whig instincts for ‘progress’ (broadly defined) manifested themselves in terms of social and economic, and what can now be considered environmental, change. As this essay will show, Palmerston's career as an Irish landlord represents an interesting case study of environmental ‘conquest’, in which nature—including also human nature—was seen as something to be mastered, controlled, and even improved. As an initially reluctant, or hesitant, landlord, who did not visit his estates in Dublin and, more substantially, those in Sligo during the first six years of his proprietorship, Palmerston ultimately set out to transform their physical environment in order to advance his broader socio-political and economic goals of making his Irish estates profitable and secure. Alongside his battles with religious groups, government agencies, and local notables in pursuit of the reform of his estates, there is also an important story to be told about how his conquest of nature suggests the ways in which the Irish landscape was, and could be, understood or regarded by this particular Victorian politician and how this reflected prevailing attitudes.
Palmerston rarely referred directly in his correspondence and notebooks to ways in which his view of nature underpinned his approach to estate management. A rare example—if it is indeed an example—is a letter from 1843 in which he told his brother:
I have been busy reading books on agriculture & horticulture & trying to acquire some knowledge on those matters which are now become sciences. If one does not know something of them oneself one can never hope to get one's estate or garden well managed. I have let all my farms at Broadlands that were out of lease, & tolerably well in spite of the badness of the times. I had a shocking set of bad tenants, but have got rid of most of them, & have brought in people with skill & capital.
Georgia Lee Tatum explained that she was not a “Republican Yankee” when she sent the manuscript of Disloyalty in the Confederacy (1934) to the University of North Carolina Press. To the contrary, her Missouri grandparents came from Virginian roots, were slaveholders, and had supported the Confederacy. Tatum was acutely aware that her topic of Southern dissent was highly controversial, if not taboo, in the Jim Crow South. The press shared her concern and required a $500 subsidy before publication. Nonetheless, Tatum’s important monograph contributed to a revisionist historiography that stressed internal opposition toward the Confederacy, strongest among those who did not own slaves, which challenged the dominant Lost Cause myth of Southern white unity.