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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Relapse prevention strategies based on monitoring of early warning signs (EWS) are advocated for the management of psychosis. However, there has been a lack of research exploring how staff, carers and patients make sense of the utility of EWS, or how these are implemented in context.
To develop a multiperspective theory of how EWS are understood and used, which is grounded in the experiences of mental health staff, carers and patients.
Twenty-five focus groups were held across Glasgow and Melbourne (EMPOWER Trial, ISRCTN: 99559262). Participants comprised 88 mental health staff, 21 patients and 40 carers from UK and Australia (total n = 149). Data were analysed using constructivist grounded theory.
All participants appeared to recognise EWS and acknowledged the importance of responding to EWS to support relapse prevention. However, recognition of and acting on EWS were constructed in a context of uncertainty, which appeared linked to risk appraisals that were dependent on distinct stakeholder roles and experiences. Within current relapse management, a process of weighted decision-making (where one factor was seen as more important than others) described how stakeholders weighed up the risks and consequences of relapse alongside the risks and consequences of intervention and help-seeking.
Mental health staff, carers and patients speak about using EWS within a weighted decision-making process, which is acted out in the context of relationships that exist in current relapse management, rather than an objective response to specific signs and symptoms.
The extent of social isolation experienced by people living with dementia who reside in the community has been well acknowledged, yet little is known about how people living alone with dementia maintain neighbourhood-based connections. The purpose of this study is to examine the experiences of people with dementia who live alone, focusing upon how they establish social networks and relationships in a neighbourhood context, and how they are supported to maintain this social context within everyday life. Multiple data collection methods were used including, semi-structured interviews, walking interviews, guided home tours and social network mapping, which were conducted with 14 community-dwelling people living alone with dementia (11 women and three men) situated across the three international study sites in England, Scotland and Sweden. Data were analysed using thematic analysis. The analysis revealed four main themes: (a) making the effort to stay connected; (b) befriending by organisations and facilitated friendships; (c) the quiet neighbourhood atmosphere; and (d) changing social connections. The analysis suggests that people with dementia who live alone were active agents who took control to find and maintain relationships and social networks in the neighbourhood. Our findings indicate the need to raise awareness about this specific group in both policy and practice, and to find creative ways to help people connect through everyday activities and by spontaneous encounters in the neighbourhood.
Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice.
To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions.
Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18–65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment.
From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI − €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI −€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI − €2075 to €41 931).
Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.
The diurnal feeding patterns of dairy cows affects the 24 h robot utilisation of pasture-based automatic milking systems (AMS). A decline in robot utilisation between 2400 and 0600 h currently occurs in pasture-based AMS, as cow feeding activity is greatly reduced during this time. Here, we investigate the effect of a temporal variation in feed quality and quantity on cow feeding behaviour between 2400 and 0600 h as a potential tool to increase voluntary cow trafficking in an AMS at night. The day was allocated into four equal feeding periods (0600 to 1200, 1200 to 1800, 1800 to 2400 and 2400 to 0600 h). Lucerne hay cubes (CP = 19.1%, water soluble carbohydrate = 3.8%) and oat, ryegrass and clover hay cubes with 20% molasses (CP = 11.8%, water soluble carbohydrate = 10.7%) were offered as the ‘standard’ and ‘preferred’ (preference determined previously) feed types, respectively. The four treatments were (1) standard feed offered ad libitum (AL) throughout 24 h; (2) as per AL, with preferred feed replacing standard feed between 2400 and 0600 h (AL + P); (3) standard feed offered at a restricted rate, with quantity varying between each feeding period (20:10:30:60%, respectively) as a proportion of the (previously) measured daily ad libitum intake (VA); (4) as per VA, with preferred feed replacing standard feed between 2400 and 0600 h (VA + P). Eight non-lactating dairy cows were used in a 4 × 4 Latin square design. During each experimental period, treatment cows were fed for 7 days, including 3 days habituation and 4 days data collection. Total daily intake was approximately 8% greater (P < 0.001) for the AL and AL + P treatments (23.1 and 22.9 kg DM/cow) as compared with the VA and VA + P treatments (21.6 and 20.9 kg DM/cow). The AL + P and VA treatments had 21% and 90% greater (P < 0.001) dry matter intake (DMI) between 2400 and 0600 h, respectively, compared with the AL treatment. In contrast, the VA + P treatment had similar DMI to the VA treatment. Our experiment shows ability to increase cow feeding activity at night by varying feed type and quantity, though it is possible that a penalty to total DMI may occur using VA. Further research is required to determine if the implementation of variable feed allocation on pasture-based AMS farms is likely to improve milking robot utilisation by increasing cow feeding activity at night.
To describe the body size and weight, and the nutrition and activity behaviours of sexual and gender minority (SGM) students and compare them with those of exclusively opposite-sex-attracted cisgender students. Male and female SGM students were also compared.
Data were from a nationally representative health survey.
Secondary schools in New Zealand, 2012.
A total of 7769 students, 9 % were SGM individuals.
Overall, weight-control behaviours, poor nutrition and inactivity were common and, in many cases, more so for SGM students. Specifically, male SGM students (adjusted OR; 95 % CI) were significantly more likely to have tried to lose weight (1·95; 1·47, 2·59), engage in unhealthy weight control (2·17; 1·48, 3·19), consume fast food/takeaways (2·89; 2·01, 4·15) and be physically inactive (2·54; 1·65, 3·92), and were less likely to participate in a school sports team (0·57; 0·44, 0·75), compared with other males. Female SGM students (adjusted OR; 95 % CI) were significantly more likely to engage in unhealthy weight control (1·58; 1·20, 2·08), be overweight or obese (1·24; 1·01, 1·53) and consume fast food/takeaways (2·19; 1·59, 3·03), and were less likely to participate in a school sports team (0·62; 0·50, 0·76), compared with other females. Generally, female SGM students were more negatively affected than comparable males, except they were less likely to consume fast food/takeaways frequently (adjusted OR; 95 % CI: 0·62; 0·40, 0·96).
SGM students reported increased weight-control behaviours, poor nutrition and inactivity. Professionals, including public health nutritionists, must recognize and help to address the challenges facing sexual and gender minorities.
The Erasmus Plus programme ‘Innovative Education and Training in high power laser plasmas’, otherwise known as PowerLaPs, is described. The PowerLaPs programme employs an innovative paradigm in that it is a multi-centre programme where teaching takes place in five separate institutes with a range of different aims and styles of delivery. The ‘in class’ time is limited to four weeks a year, and the programme spans two years. PowerLaPs aims to train students from across Europe in theoretical, applied and laboratory skills relevant to the pursuit of research in laser–plasma interaction physics and inertial confinement fusion (ICF). Lectures are intermingled with laboratory sessions and continuous assessment activities. The programme, which is led by workers from the Technological Educational Institute (TEI) of Crete, and supported by co-workers from the Queen’s University Belfast, the University of Bordeaux, the Czech Technical University in Prague, Ecole Polytechnique, the University of Ioannina, the University of Salamanca and the University of York, has just completed its first year. Thus far three Learning Teaching Training (LTT) activities have been held, at the Queen’s University Belfast, the University of Bordeaux and the Centre for Plasma Physics and Lasers (CPPL) of TEI Crete. The last of these was a two-week long Intensive Programme (IP), while the activities at the other two universities were each five days in length. Thus far work has concentrated upon training in both theoretical and experimental work in plasma physics, high power laser–matter interactions and high energy density physics. The nature of the programme will be described in detail and some metrics relating to the activities carried out to date will be presented.
Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated.
We used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods.
Bacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%–14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change.
Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.
Achieving a consistent level of robot utilisation throughout 24 h maximises automatic milking system (AMS) utilisation. However, levels of robot utilisation in the early morning hours are typically low, caused by the diurnal feeding behaviour of cows, limiting the inherent capacity and total production of pasture-based AMS. Our objective was to determine robot utilisation throughout 24 h by dairy cows, based on milking frequency (MF; milking events per animal per day) in a pasture-based AMS. Milking data were collected from January and February 2013 across 56 days, from a single herd of 186 animals (Bos taurus) utilising three Lely A3 robotic milking units, located in Tasmania, Australia. The dairy herd was categorised into three equal sized groups (n=62 per group) according to the cow’s mean daily MF over the duration of the study. Robot utilisation was characterised by an interaction (P< 0.001) between the three MF groups and time of day, with peak milking time for high MF cows within one h of a fresh pasture allocation becoming available, followed by the medium MF and low MF cows 2 and 4 h later, respectively. Cows in the high MF group also presented for milking between 2400 and 0600 h more frequently (77% of nights), compared to the medium MF group (57%) and low MF group (50%). This study has shown the formation of three distinct groups of cows within a herd, based on their MF levels. Further work is required to determine if this finding is replicated across other pasture-based AMS farms.
Two burials excavated at Izapa in 1963 have special green obsidian artifacts made at Teotihuacan. We describe the contexts and contents of these burials and consider the significance of their contents in light of Spence's (1996) model of Teotihuacan exchange of obsidian objects. We interpret the Izapa artifacts as gifted objects indicative of the political independence of Izapa in Middle Classic times.
Fecal samples from wild-caught common voles (n = 328) from 16 locations in the Czech Republic were screened for Cryptosporidium by microscopy and PCR/sequencing at loci coding small-subunit rRNA, Cryptosporidium oocyst wall protein, actin and 70 kDa heat shock protein. Cryptosporidium infections were detected in 74 voles (22.6%). Rates of infection did not differ between males and females nor between juveniles and adults. Phylogenetic analysis revealed the presence of eight Cryptosporidium species/genotypes including two new species, C. alticolis and C. microti. These species from wild-caught common voles were able to infect common and meadow voles under experimental conditions, with a prepatent period of 3–5 days post-infection (DPI), but they were not infectious for various other rodents or chickens. Meadow voles lost infection earlier than common voles (11–14 vs 13–16 DPI) and had significantly lower infection intensity. Cryptosporidium alticolis infects the anterior small intestine and has larger oocysts (5.4 × 4.9 µm), whereas C. microti infects the large intestine and has smaller oocysts (4.3 × 4.1 µm). None of the rodents developed clinical signs of infection. Genetic and biological data support the establishment of C. alticolis and C. microti as separate species of the genus Cryptosporidium.
Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
Current policy emphasises the importance of ‘living well’ with dementia, but there has been no comprehensive synthesis of the factors related to quality of life (QoL), subjective well-being or life satisfaction in people with dementia. We examined the available evidence in a systematic review and meta-analysis. We searched electronic databases until 7 January 2016 for observational studies investigating factors associated with QoL, well-being and life satisfaction in people with dementia. Articles had to provide quantitative data and include ⩾75% people with dementia of any type or severity. We included 198 QoL studies taken from 272 articles in the meta-analysis. The analysis focused on 43 factors with sufficient data, relating to 37639 people with dementia. Generally, these factors were significantly associated with QoL, but effect sizes were often small (0.1–0.29) or negligible (<0.09). Factors reflecting relationships, social engagement and functional ability were associated with better QoL. Factors indicative of poorer physical and mental health (including depression and other neuropsychiatric symptoms) and poorer carer well-being were associated with poorer QoL. Longitudinal evidence about predictors of QoL was limited. There was a considerable between-study heterogeneity. The pattern of numerous predominantly small associations with QoL suggests a need to reconsider approaches to understanding and assessing living well with dementia.
Comprising Holostei and Teleostei, the ~32,000 species of neopterygian fishes are anatomically disparate and represent the dominant group of aquatic vertebrates today. However, the pattern by which teleosts rose to represent almost all of this diversity, while their holostean sister-group dwindled to eight extant species and two broad morphologies, is poorly constrained. A geometric morphometric approach was taken to generate a morphospace from more than 400 fossil taxa, representing almost all articulated neopterygian taxa known from the first 150 million years—roughly 60%—of their history (Triassic‒Early Cretaceous). Patterns of morphospace occupancy and disparity are examined to: (1) assess evidence for a phenotypically “dominant” holostean phase; (2) evaluate whether expansions in teleost phenotypic variety are predominantly abrupt or gradual, including assessment of whether early apomorphy-defined teleosts are as morphologically conservative as typically assumed; and (3) compare diversification in crown and stem teleosts. The systematic affinities of dapediiforms and pycnodontiforms, two extinct neopterygian clades of uncertain phylogenetic placement, significantly impact patterns of morphological diversification. For instance, alternative placements dictate whether or not holosteans possessed statistically higher disparity than teleosts in the Late Triassic and Jurassic. Despite this ambiguity, all scenarios agree that holosteans do not exhibit a decline in disparity during the Early Triassic‒Early Cretaceous interval, but instead maintain their Toarcian‒Callovian variety until the end of the Early Cretaceous without substantial further expansions. After a conservative Induan‒Carnian phase, teleosts colonize (and persistently occupy) novel regions of morphospace in a predominantly gradual manner until the Hauterivian, after which expansions are rare. Furthermore, apomorphy-defined teleosts possess greater phenotypic variety than typically assumed. Comparison of crown and stem teleost partial disparity indicates that, despite a statistically significant increase in crown teleost disparity between the Late Jurassic and earliest Cretaceous, stem teleosts remained important long-term contributors to overall teleost disparity during this time.
The salon at Holland House, presided over by the formidable Lady Holland herself, is well known as a major institution in British political and cultural history. It is rightly regarded as at least as important as the rival salons of Dorothea Lieven and the Duchess of Dino. Anecdotes abound – for example, the occasion when Lady Holland sent a note to T. B. Macaulay asking him not to dominate the conversation. But the conversation then flagged and Lady Holland was forced to send another note to Macaulay which read ‘Please do dominate the conversation Mr. Macaulay.’ The salon was at its most influential in the 1820s and 1830s, with Lord and Lady Holland – Lord Holland was the nephew of Charles James Fox – seen as the guardians of the pure traditions of English Whiggery.
Perhaps the most important element in the Whig tradition was a belief in the importance of aristocracy, literally ‘the rule of the best’. The role of a properly enlightened aristocracy was to place strict limits on the powers of absolutist- inclined monarchs and to provide leadership to the rest of society to protect it from the allure of demagogues and extreme radicals. The institutional embodiment of these principles was, of course, a parliament, but a parliament consisting of two chambers with the upper chamber largely composed of hereditary peers. In some respects, Whiggery was an ideology rooted in the England of the late seventeenth and eighteenth centuries. Long years of exclusion from office, coupled with a recognition that significant social and economic change was occurring, added a new dimension to the strategy – a readiness to enrol the new middle classes as junior partners in a sort of progressive coalition. Above all, this found expression in the Reform Bill of 1832. Whigs believed in religious toleration and were often somewhat sceptical about conventional religious beliefs; many were Freemasons. Within fairly broad limits, they believed in a free press and the rule of law. Although not completely identical, Whigs might be regarded as the precursors of later Liberals.
But Holland House stood for something more; it had a significant international dimension. In short, Lord and Lady Holland wanted to promote the development of societies and political systems based upon their own principles elsewhere in the world.