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The two-dot-plus-bar ‘distigme-obelos’ symbols in Vaticanus signal added text. Five characteristic features distinguish their obeloi from paragraphoi. Like scribe B's LXX obeloi, all eight distigme-obelos symbols mark the location of added text. A gap at the exact location of a widely recognised, multi-word addition follows every distigme-obelos except one with distinctive downward dipping strokes. The Vaticanus Gospels are so early that they have virtually no high stops, a feature older than even 75. Consequently, they contain none of these additions, but the Vaticanus epistles have high stops throughout and contain their one distigme-obelos-marked addition, 1 Cor 14.34–5. Contemporaneous LXX G has corresponding distigmai.
The Earth's atmosphere and the Earth's magnetic field protects local life by shielding us against Solar particle flows, just like the sun's magnetic field deflects cosmic particle radiation. Generally, magnetic fields can affect terrestrial life such as migrating animals. Thus, terrestrial life is connected to astronomical interrelations between different magnetic fields, particle flows and radiation. Mass strandings of whales have often been documented, but their causes and underlying mechanisms remain unclear. We investigated the possible reasons for this phenomenon based on a series of strandings of 29 male, mostly bachelor, sperm whales (Physeter macrocephalus) in the southern North Sea in early 2016. Whales’ magnetic sense may play an important role in orientation and migration, and strandings may thus be triggered by geomagnetic storms. This approach is supported by the following: (1) disruptions of the Earth's magnetic field by Solar storms can last about 1 day and lead to short-term magnetic latitude changes corresponding to shifts of up to 460 km; (2) many of these disruptions are of a similar magnitude to more permanent geomagnetic anomalies; (3) geomagnetic anomalies in the area north of the North Sea are 50–150 km in diameter; and (4) sperm whales swim about 100 km day−1, and may thus be unable to distinguish between these phenomena. Sperm whales spend their early, non-breeding years in lower latitudes, where magnetic disruptions by the sun are weak and thus lack experience of this phenomenon. ‘Naïve’ whales may therefore become disoriented in the southern Norwegian Sea as a result of failing to adopt alternative navigation systems in time and becoming stranded in the shallow North Sea.
According to a systematic review on the use of selective serotonin reuptake inhibitors (SSRIs) in adult depression that was recently published in BMC Psychiatry, the results of which have been widely disseminated in lay media, these drugs increase the risk for serious adverse events (SAEs) while exerting poor antidepressant efficacy. A cursory analysis, however, suggests the analysis of SAEs conducted by the authors to be marred by both methodological inaccuracies and blatant errors. After having corrected for these apparent mistakes, we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age; while this suggests SSRIs to be safe drugs in the non-elderly, they do confirm what is already known, that is, that they may enhance the risk for SAEs in the old. Given the loose definition of SAE, including also innocuous phenomena, the possible clinical significance of the latter observation, however, remains unclear until the nature and actual impact of the SAEs in question have been clarified. Moreover, with respect to efficacy, we find the paper in BMC Psychiatry misleading: first, the authors seem unaware of the well-established shortcomings associated with the conventional efficacy parameter on which their analysis is based, second, they have included suboptimal SSRI doses and third, they have missed some pivotal trials. Unless there are explanations for the many peculiarities in this paper that have escaped us, and which may be satisfactorily clarified by the authors, it seems important that the conclusions presented in this paper be publicly rectified.
This article describes a formal proof of the Kepler conjecture on dense sphere packings in a combination of the HOL Light and Isabelle proof assistants. This paper constitutes the official published account of the now completed Flyspeck project.
Taylor Glacier hosts an active englacial hydrologic system that feeds Blood Falls, a supraglacial outflow of iron-rich subglacial brine at the terminus, despite mean annual air temperatures of −17°C and limited surface melt. Taylor Glacier is an outlet glacier of the East Antarctic ice sheet that terminates in Lake Bonney, McMurdo Dry Valleys. To image and map the brine feeding Blood Falls, we used radio echo sounding to delineate a subhorizontal zone of englacial brine upstream from Blood Falls and elongated in the ice flow direction. We estimate volumetric brine content in excess of 13% within 2 m of the central axis of this zone, and likely much higher at its center. Brine content decreases, but remains detectable, up to 45 m away along some transects. Hence, we infer a network of subparallel basal crevasses allowing injection of pressurized subglacial brine into the ice. Subglacial brine is routed towards Blood Falls by hydraulic potential gradients associated with deeply incised supraglacial valleys. The brine remains liquid within the subglacial and englacial environments through latent heat of freezing coupled with elevated salt content. Our findings suggest that cold glaciers could support freshwater hydrologic systems through localized warming by latent heat alone.
Social impact bonds are payment by results contracts that leverage private social investment to cover the up-front expenditure associated with welfare services. The introduction of private principles and actors through outcome-based commissioning has received a great deal of attention in social policy research. However, there has been much less attention given to the introduction of private capital and its relation to more established forms of quasi-marketisation. This paper examines what effect private social investment has on outcome-based commissioning and whether the alternative forms of performance measurement and management, that social impact bonds bring to bear on service operations, demonstrate the capacity to engender: innovation in service delivery; improved social outcomes; future cost savings; and additionality. This paper draws on an in-depth study of four social impact bonds in the UK context, as the welfare regime at the vanguard of this policy development. The findings suggest that the introduction of private capital in outcome-based commissioning has had a number of unique and unintended effects on service providers, operations and outcomes. The paper concludes by considering whether social impact bonds represent a risk or an opportunity for public service reform both in the UK and further afield.
Recent genetic, isotopic and linguistic research has dramatically changed our understanding of how the Corded Ware Culture in Europe was formed. Here the authors explain it in terms of local adaptations and interactions between migrant Yamnaya people from the Pontic-Caspian steppe and indigenous North European Neolithic cultures. The original herding economy of the Yamnaya migrants gradually gave way to new practices of crop cultivation, which led to the adoption of new words for those crops. The result of this hybridisation process was the formation of a new material culture, the Corded Ware Culture, and of a new dialect, Proto-Germanic. Despite a degree of hostility between expanding Corded Ware groups and indigenous Neolithic groups, stable isotope data suggest that exogamy provided a mechanism facilitating their integration. This article should be read in conjunction with that by Heyd (2017, in this issue).
The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14–16 weeks’ gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24–30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks’ gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.
Mental health problems are inseparable from the environment. With virtual reality (VR), computer-generated interactive environments, individuals can repeatedly experience their problematic situations and be taught, via evidence-based psychological treatments, how to overcome difficulties. VR is moving out of specialist laboratories. Our central aim was to describe the potential of VR in mental health, including a consideration of the first 20 years of applications. A systematic review of empirical studies was conducted. In all, 285 studies were identified, with 86 concerning assessment, 45 theory development, and 154 treatment. The main disorders researched were anxiety (n = 192), schizophrenia (n = 44), substance-related disorders (n = 22) and eating disorders (n = 18). There are pioneering early studies, but the methodological quality of studies was generally low. The gaps in meaningful applications to mental health are extensive. The most established finding is that VR exposure-based treatments can reduce anxiety disorders, but there are numerous research and treatment avenues of promise. VR was found to be a much-misused term, often applied to non-interactive and non-immersive technologies. We conclude that VR has the potential to transform the assessment, understanding and treatment of mental health problems. The treatment possibilities will only be realized if – with the user experience at the heart of design – the best immersive VR technology is combined with targeted translational interventions. The capability of VR to simulate reality could greatly increase access to psychological therapies, while treatment outcomes could be enhanced by the technology's ability to create new realities. VR may merit the level of attention given to neuroimaging.
The expanding reach of international investment law and the negotiation of major economic treaties between democratic polities have prompted new debates about the relationship between democracy and the international investment regime. This article develops an analytical framework for understanding that relationship. It first unpacks the concept of democracy, exploring the ‘rules-based’ and ‘action-based’ conceptions that emerge from political theory and their relevance to international investment law. It then examines three themes that frame the relationship between democracy and international investment law: the interface between the investment regime and national democratic space; the place of democratic processes in investment treaty making; and public participation in the settlement of investment disputes. The interplay between rules- and action-based dimensions provides a common thread across the three themes. The article concludes that there is a gap between formal rules and citizen action in promoting democratic oversight, and significant scope to develop more effective mechanisms to install democratic governance in the creation and implementation of international investment law.
A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.
Congenital or early life infection with Toxoplasma gondii has been implicated in schizophrenia aetiology. Childhood cat ownership has been hypothesized as an intermediary marker of T. gondii infection and, by proxy, as a risk factor for later psychosis. Evidence supporting this hypothesis is, however, limited.
Method
We used birth cohort data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate whether cat ownership in pregnancy and childhood (ages 4 and 10 years) was associated with psychotic experiences (PEs) in early (age 13, N = 6705) and late (age 18, N = 4676) adolescence, rated from semi-structured interviews. We used logistic regression to examine associations between cat ownership and PEs, adjusting for several sociodemographic and socioeconomic factors, household characteristics and dog ownership. Missing data were handled via multiple imputation.
Results
Cat ownership during pregnancy was not associated with PEs at age 13 years [adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 0.97–1.35] or 18 years (OR 1.08, 95% CI 0.86–1.35). Initial univariable evidence that cat ownership at ages 4 and 10 years was associated with PEs at age 13 years did not persist after multivariable adjustment (4 years: OR 1.18, 95% CI 0.94–1.48; 10 years: OR 1.12, 95% CI 0.92–1.36). There was no evidence that childhood cat ownership was associated with PEs at age 18 years.
Conclusions
While pregnant women should continue to avoid handling soiled cat litter, given possible T. gondii exposure, our study strongly indicates that cat ownership in pregnancy or early childhood does not confer an increased risk of later adolescent PEs.
Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chemical and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is one of the major aetiological factors associated with several gastrointestinal diseases, including infection by pathogens, obesity and diabetes, necrotising enterocolitis, irritable bowel syndrome and inflammatory bowel disease. The notion that specific probiotic bacterial strains can affect barrier integrity fuelled research in which in vitro cell lines, animal models and clinical trials are used to assess whether probiotics can revert the diseased state back to homeostasis and health. This review catalogues and categorises the lines of evidence available in literature for the role of probiotics in epithelial integrity and, consequently, their beneficial effect for the reduction of gastrointestinal disease symptoms.
Observational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data.
Method
We performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10−5) and schizophrenia (p < 5 × 10−8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses.
Results
There was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01–1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05–1.14, p = 2.64 × 10−5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99–1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97–1.00, p = 0.066) analyses.
Conclusions
Our results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.
It is well established that when a turbulent flow is subjected to a non-uniform body force, the turbulence may be significantly suppressed in comparison with that of the flow of the same flow rate and hence the flow is said to be laminarised. This is the situation in buoyancy-aided mixed convection when severe heat transfer deterioration may occur. Here we report results of direct numerical simulations of flow with a linear or a step-change profile of body force. In contrast to the conventional view, we show that applying a body force to a turbulent flow while keeping the pressure force unchanged causes little changes to the key characteristics of the turbulence. In particular, the mixing characteristics of the turbulence represented by the turbulent viscosity remain largely unaffected. The so-called flow laminarisation due to a body force is in effect a reduction in the apparent Reynolds number of the flow, based on an apparent friction velocity associated with only the pressure force of the flow (i.e. excluding the contribution of the body force). The new understanding allows the level of the flow ‘laminarisation’ and when the full laminarisation occurs to be readily predicted. In terms of the near-wall turbulence structure, the numbers of ejections and sweeps are little influenced by the imposition of the body force, whereas the strength of each event may be enhanced if the coverage of the body force extends significantly away from the wall. The streamwise turbulent stress is usually increased in accordance with the observation of more and stronger elongated streaks, but the wall-normal and the circumferential turbulent stresses are largely unchanged.
Geophysical granular flows, such as landslides, pyroclastic flows and snow avalanches, consist of particles with varying surface roughnesses or shapes that have a tendency to segregate during flow due to size differences. Such segregation leads to the formation of regions with different frictional properties, which in turn can feed back on the bulk flow. This paper introduces a well-posed depth-averaged model for these segregation-mobility feedback effects. The full segregation equation for dense granular flows is integrated through the avalanche thickness by assuming inversely graded layers with large particles above fines, and a Bagnold shear profile. The resulting large particle transport equation is then coupled to depth-averaged equations for conservation of mass and momentum, with the feedback arising through a basal friction law that is composition dependent, implying greater friction where there are more large particles. The new system of equations includes viscous terms in the momentum balance, which are derived from the $\unicode[STIX]{x1D707}(I)$-rheology for dense granular flows and represent a singular perturbation to previous models. Linear stability calculations of the steady uniform base state demonstrate the significance of these higher-order terms, which ensure that, unlike the inviscid equations, the growth rates remain bounded everywhere. The new system is therefore mathematically well posed. Two-dimensional simulations of bidisperse material propagating down an inclined plane show the development of an unstable large-rich flow front, which subsequently breaks into a series of finger-like structures, each bounded by coarse-grained lateral levees. The key properties of the fingers are independent of the grid resolution and are controlled by the physical viscosity. This process of segregation-induced finger formation is observed in laboratory experiments, and numerical computations are in qualitative agreement.
Most discussions of racial fetish center on the question of whether it is caused by negative racial stereotypes. In this paper I adopt a different strategy, one that begins with the experiences of those targeted by racial fetish rather than those who possess it; that is, I shift focus away from the origins of racial fetishes to their effects as a social phenomenon in a racially stratified world. I examine the case of preferences for Asian women, also known as ‘yellow fever’, to argue against the claim that racial fetishes are unobjectionable if they are merely based on personal or aesthetic preference rather than racial stereotypes. I contend that even if this were so, yellow fever would still be morally objectionable because of the disproportionate psychological burdens it places on Asian and Asian-American women, along with the role it plays in a pernicious system of racial social meanings.
Prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasingly and is a key risk for CVD development, now recognised as the leading cause of death globally. Dietary strategies to reduce CVD development include reduction of saturated fat intake. Milk and dairy products are the largest contributors to dietary saturated fats in the UK and reduced consumption is often recommended as a strategy for risk reduction. However, overall evidence from prospective cohort studies does not confirm a detrimental association between dairy product consumption and CVD risk. The present review critically evaluates the current evidence on the association between milk and dairy products and risk of CVD, T2DM and the metabolic syndrome (collectively, cardiometabolic disease). The effects of total and individual dairy foods on cardiometabolic risk factors and new information on the effects of the food matrix on reducing fat digestion are also reviewed. It is concluded that a policy to lower SFA intake by reducing dairy food consumption to reduce cardiometabolic disease risk is likely to have limited or possibly negative effects. There remain many uncertainties, including differential effects of different dairy products and those of differing fat content. Focused and suitably designed and powered studies are needed to provide clearer evidence not only of the mechanisms involved, but how they may be beneficially influenced during milk production and processing.
By all accounts, 2016 is the year of the chatbot. Some commentators take the view that chatbot technology will be so disruptive that it will eliminate the need for websites and apps. But chatbots have a long history. So what's new, and what's different this time? And is there an opportunity here to improve how our industry does technology transfer?
This paper presents the results of a multidisciplinary project that has revealed the location, extent and character of the winter camp of the Viking Great Army at Torksey, Lincolnshire, of ad 872–3. The camp lay within a naturally defended area of higher ground, partially surrounded by marshes and bordered by the River Trent on its western side. It is considerably larger than the Viking camp of 873–4 previously excavated at Repton, Derbyshire, and lacks the earthwork defences identified there. Several thousand individuals overwintered in the camp, including warriors, craftworkers and merchants. An exceptionally large and rich metalwork assemblage was deposited during the Great Army’s overwintering, and metal processing and trading was undertaken. There is no evidence for a pre-existing Anglo-Saxon trading site here; the site appears to have been chosen for its strategic location and its access to resources. In the wake of the overwintering, Torksey developed as an important Anglo-Saxon borough with a major wheel-thrown pottery industry and multiple churches and cemeteries. The Torksey evidence allows for a radical reappraisal of the character of Viking winter camps, and the legacy of the Viking Great Army for Anglo-Saxon England.