It is becoming increasingly apparent that sleep plays an important role in the maintenance, disease prevention, repair, and restoration of both mind and body. The sleep and wake cycles are controlled by the pacemaker activity of the superchiasmic nucleus in the hypothalamus but can be disrupted by diseases of the nervous system causing disordered sleep. A lack of sleep has been associated with an increase in all-cause mortality. Likewise, sleep disturbances and sleep disorders may disrupt neuronal pathways and have an impact on neurological diseases. Sleep deprivation studies in normal subjects demonstrate that a lack of sleep can cause attention and working memory impairment. Moreover, untreated sleep disturbances and sleep disorders such as obstructive sleep apnoe (OSA) can also lead to cognitive impairment. Poor sleep and sleep disorders may present a significant risk factor for the development of dementia. In this review, the underlying mechanisms and the role of sleep and sleep disorders in the development of neurocognitive disorders [dementia and mild cognitive impairment (MCI)] and how the presence of sleep disorders could direct the process of diagnosis and management of neurocognitive disorders will be discussed.
Objectives: To assess the longitudinal evidence of the relationships between sleep disturbances (of quantity and quality) and dyslipidaemia in the general population and to quantify such relationships.
Setting: Systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Methods: We performed a systematic search of PubMed and Embase (up to 9 September 2017), complemented with manual searches, of prospective population studies describing the association between sleep duration and quality and the incidence of dyslipidaemias. Relative risks (95% CIs) were extracted and pooled using a random effects model. Subgroup analyses by lipid type were performed. Heterogeneity and publication bias were also assessed. Quality was assessed with Downs and Black score.
Participants: Studies were included if they were prospective, had measured sleep quantity and/or quality at baseline and either incident cases of dyslipidaemia or changes in blood lipid fractions assessed prospectively.
Primary outcome measures: Incidence of dyslipidaemia and changes in lipid fractions. Dyslipidaemia was defined as a high total cholesterol, triglycerides, low-density lipoprotein cholesterol or low high-density lipoprotein cholesterol compared with the reference group.
Results: Thirteen studies were identified (eight using sleep duration, four sleep quality and one both). There was heterogeneity in the sleep quality aspects and types of lipids assessed. Classification of sleep duration (per hour/groups) also varied widely. In the pooled analysis of sleep duration (6 studies, 16 cohort samples; 30 033 participants; follow-up 2.6–10 years), short sleep was associated with a risk of 1.01 (95% CI 0.93 to 1.10) of developing dyslipidaemia, with moderate heterogeneity (I2=56%, P=0.003) and publication bias (P=0.035). Long sleep was associated with a risk of 0.98 (95% CI 0.87 to 1.10) for dyslipidaemia, with heterogeneity (I2=63%, P<0.001) and no significant publication bias (P=0.248).
Conclusion: The present analysis was unable to find supportive evidence of a significant relationship between sleep duration and the development of dyslipidaemia. However, heterogeneity and small number of studies limit the interpretation.
In Happiness for All?, Carol Graham raises disquieting ideas about today's United States. The challenge she puts forward is an important one. Here we review the intellectual case and offer additional evidence. We conclude broadly on the author's side. Strikingly, Americans appear to be in greater pain than citizens of other countries, and most subgroups of citizens have downwardly trended happiness levels. There is, however, one bright side to an otherwise dark story. The happiness of black Americans has risen strongly since the 1970s. It is now almost equal to that of white Americans.
This article reviews Bayesian inference methods for Vector Autoregression models, commonly used priors for economic and financial variables, and applications to structural analysis and forecasting.
Ageing prediction is often complicated due to the interdependency of ageing mechanisms. Research has highlighted that storage ageing is not linear with time. Capacity loss due to storing the battery at constant temperature can shed more light on parametrising the properties of the Solid Electrolyte Interphase (SEI); the identification of which, using an electrochemical model, is systematically addressed in this work. A new methodology is proposed where any one of the available storage ageing datasets can be used to find the property of the SEI layer. A sensitivity study is performed with different molecular mass and densities which are key parameters in modelling the thickness of the SEI deposit. The conductivity is adjusted to fine tune the rate of capacity fade to match experimental results. A correlation is fitted for the side reaction variation to capture the storage ageing in the 0%–100% SoC range. The methodology presented in this paper can be used to predict the unknown properties of the SEI layer which is difficult to measure experimentally. The simulation and experimental results show that the storage ageing model shows good accuracy for the cases at 50% and 90% and an acceptable agreement at 20% SoC.
This book explores the paradoxical place of enthusiasm in Dryden's writing and the role he conceived for it in art and society after the violent upheavals of the mid seventeenth century. Works from across his oeuvre are explored, from his early essays and heroic plays to his translations, via new readings of his famous political and religious poems. These are read alongside other major writers of the period, like Milton, and less well-known authors, such as John Dennis. The book suggests new ways of conceptualising the relationship between literary practice and ideological allegiance in Restoration England. It reveals Dryden to be a writer who was consistently interested in the limits of what literature could express, what feelings it could provoke, and what it could make people believe at a time when such questions were of uncertain political importance.
Summary: Literature of the Stuart Successions" is an anthology of primary material relating to the Stuart successions. The six Stuart successions (1603, 1625, 1660, 1685, 1688-9, 1702) punctuate this turbulent period of British history. In addition, there were two accessions to the role of Lord Protector (those of Oliver and Richard Cromwell). Each succession generated an outpouring of publications in a wide range of forms and genres, including speeches, diary-entries, news reports, letters and sermons. Above all, successions were marked in poems, by some of the greatest writers of the age. By gathering together some of the very best Stuart succession writing, Literature of the Stuart Successions offers fresh perspectives upon the history and culture of the period. It includes fifty texts (or extracts), selected to demonstrate the breadth and significance of succession writing, as well as introductory and explanatory material.
This dissertation argues that insects provided a crucial lens through which Enlightenment thinkers could reimagine and represent their societies. It demomstrates that the understanding of the functioning of their individual bodies, the close observation of their collective behaviour, and its manipulation and management, helped eighteenth-century scholars to conceptualise, and root in nature, their social orders and the changes that they wished to see in them. While insect collectives such as bee swarms or ant colonies that had long been used to metaphorically model human societies, in the eighteenth century, these metaphors were reformulated and given an empirical basis.
Investigating writings on insects on the part of natural historians, agronomists, philosophes and physicians, the thesis contributes to the growing literature on the role of animals in human history in general and in the Enlightenment in particular. It builds on two scholarly traditions: French studies and the cultural history of scientific, economic and political knowledge (mainly written after the 1980s). I take from French studies methods for the close reading of texts and more recent ideas on how 'to bridge' different fields of knowledge; the latter discipline will be useful in providing ideas about the history of observation and experimentation, theories of the animal and human body as well as eighteenth-century understanding of political economy. As this dissertation demonstrates, insects helped conceptualise new ideas of the human individual and his or her passions (chapters 1 and 2), of how human collectives are formed (chapter 3) and how governments can manipulate and regulate them in the most profitable ways possible (chapters 4 and 5). By investigating Enlightenment writings on insects, this thesis shows, we can recover part of the rich history of our modern understanding of our own ways of living together.
We develop a non-parametric test for consistency of player behavior with the Quantal Re- sponse Equilibrium (QRE). The test exploits a characterization of the equilibrium choice prob- abilities in any structural QRE as the gradient of a convex function; thereby QRE-consistent choices satisfy the cyclic monotonicity inequalities. Our testing procedure utilizes recent econo- metric results for moment inequality models. We assess our test using lab experimental data from a series of generalized matching pennies games. We reject the QRE hypothesis in the pooled data but cannot reject individual-level quantal response behavior for over half of the subjects.
Direct numerical simulations (DNS) have been performed for turbulent pipe flows using a high-order spectral element method code Nek5000. This is one of the first DNS studies of spatially developing turbulent pipe ow with a 90° bend. A turbulent inflow condition was implemented using a recycling technique. To study the unsteady oscillations of the Dean vortices, i.e., swirl switching phenomenon, the pressure force acting on the pipe wall around the bend is analysed. The lateral pressure force exhibits spatio-temporal oscillations. Conditional averaging is performed for large (positive/negative) force oscillation events to find the flow structure responsible for the force oscillation. It is found that the quasi-periodic force oscillation is closely associated with the swirl switching phenomenon. It is also observed that the mass flow rate oscillates with the swirl switching, and the frequency of this oscillation is found to be about St 0:5. 3D conditional averaging analysis reveals that the travelling wave-like three-dimensional ow structures are responsible for the spatio-temporal oscillations of the pressure force.
Effects of the bend curvature ratio and Reynolds number on the flow recovery downstream of the bend and the swirl switching phenomenon are investigated. Both mild and sharp pipe bends were considered. Clear dependence on the curvature ratio are observed for various key flow properties, including pressure drop, friction factor, mean velocity profile, velocity fluctuations, etc. It is found that turbulence recovers faster downstream of a sharper bend. Conditional averaging for different curvature ratios shows that 90° bend pipe flow features an underlying travelling wave-like characteristic. The swirl switching frequency is observed to be higher when flow separation is present, whereas it appears to be not affected by the Reynolds number.
The first DNS has been performed for a temporally accelerating turbulent pipe flow. Transient behaviour of turbulence statistics is analysed through ensemble averaging. The effect of acceleration rate on the response of turbulence is also investigated. The wall shear stress exhibits a distinctive four-stage development in the transient pipe flow. The pipe core region is found to be frozen during the initial transient stages. Turbulence starts to respond in the near-wall region first, and then propagates radially towards the pipe centre. The propagation speed is observed to be very similar among the three velocity components, and it is largely independent of the acceleration rate. During acceleration, the streamwise velocity component always responds first, followed by the other two components with a longer delay.
It is widely accepted that the Five Factor Model (FFM) is a satisfactory description of the pattern of covariations among personality traits, which supposedly fits, more or less adequately, every individual. As an amendment to the FFM, we propose that the customary five-factor structure is only a near-universal, because it does not fit all individuals but only a large majority of them. Evidences reveal a small minority of participants who have an unusual configuration of personality traits, which is clearly recognizable, both in self- and observer-ratings. We identified three types of atypical configurations of personality traits, characterized mainly by a scatter of subscale scores within each of the FFM factors. How different configurations of personality traits are formed, persist, and function needs further investigation.
This article extends the critique of H. L. A. Hart developed by Peter Fitzpatrick in the conclusion to The Mythology of Modern Law. Fitzpatrick finds myth at the very heart of positivist legal theory, functioning to reproduce an imperialist worldview. Through a focus on Hart's account of incorporation, this article will argue that Hart naturalises this mythic law by insinuating it into social relations. Incorporation, alongside other 'facilitative' or 'power-conferring' elements of law such as wills and marriages, are so important that we could not imagine life without them. At the same time, Hart maintains the importance of choice and autonomy in relation to such rules, but in so doing obscures their constitutive function. In his reliance on myth, Hart avoids contending with the history that forms the unacknowledged context for his account of incorporation. By reintroducing this history, this article demonstrates that Hart participates in the normalisation of law that Michel Foucault locates in the union between life and law that is characteristic of biopolitics.
Health information technology (IT) offers exciting opportunities for providing novel services to patients, and for improving the quality and safety of care. However, the introduction of IT can lead to unintended consequences, and create opportunities for failure, which can have significant effects on patient safety. In this paper I argue that many health IT patient safety risks are probably quite predictable, but are often not considered at the time. This puts patients at risk, and it threatens the successful adoption of health IT. I recommend that healthcare providers focus on strengthening their processes for organisational learning, promote proactive risk management strategies, and make risk management decisions transparent and explicit.
Many bacterial pathogens present adhesins at the tips of long macromolecular filaments known as pili that are often important virulence determinants. Very little is known about how pili presented by Gram-positive pathogens mediate host cell binding. The crystal structure of a pilus adhesin from the important human pathogen Streptococcus pyogenes reveals an internal thioester bond formed between the side chains of a cysteine and a glutamine residue. The presence of the thioester was verified using UV-visible spectroscopy and mass spectrometry. This unusual bond has only previously been observed in thioester domains of complement and complement-like proteins where it is used to form covalent attachment to target molecules. The structure also reveals two intramolecular isopeptide bonds, one of these formed through a Lys/Asp residue pair, which are strategically positioned to confer protein stability. Removal of the internal thioester by allele-replacement mutagenesis in S. pyogenes severely compromises bacterial adhesion to model host cells. Although current paradigms of bacterial/host cell interaction envisage strong non-covalent interactions, the present study suggests cell adhesion could also involve covalent bonds.
Composite shell linings consist of primary and secondary sprayed concrete linings separated by a layer of spray-applied waterproofing membrane. In order to design such a lining configuration, a calibrated numerical simulation approach is needed and the impact of interface properties on the composite mechanical behaviour should be understood.
A programme of laboratory tests was carried out on beam samples cut from composite shell test panels and subjected to four-point bending under short-term loading. A range of membrane thicknesses and substrate roughness were compared and composite mechanical behaviour quantification methods developed. The behaviour of composite beams was understood and the strain distribution across composite lining cross-section was identified.
A numerical model by the finite difference method was then set up for the beams and verified against the test data. With interface stiffnesses obtained from previous element tests, the composite beam model is capable of predicting the strain distribution across the cross-section and real behaviour of composite beam members to within an acceptable level of accuracy taking into account variations arising from workmanship. Sensitivity studies were carried out to understand the impact of interface properties and membrane interface position on the degree of composite action.
Objectives To investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).
Design Cross-sectional study.
Setting University Hospitals Coventry & Warwickshire NHS Trust; European Neuroendocrine Tumour Society Centre of Excellence.
Participants Patients with confirmed GEP-NET (n=161) of varying primary tumour sites, functioning status, grading, staging and treatment modalities.
Main outcome measure To identify disease and treatment-related characteristics of patients with GEP-NET who score using MUST, and should be directed to detailed nutritional assessment.
Results MUST score was positive (≥1) in 14% of outpatients with GEP-NET. MUST-positive patients had lower faecal elastase concentrations compared to MUST-negative patients (244±37 vs 383±20 µg/g stool; p=0.018), and were more likely to be on treatment with long-acting somatostatin analogues (65 vs 38%, p=0.021). MUST-positive patients were also more likely to have rectal or unknown primary NET, whereas, frequencies of other GEP-NET including pancreatic NET were comparable between MUST-positive and MUST-negative patients.
Conclusions Given the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues.
To satisfy their requirement for iron while at the same time countering the toxicity of this highly reactive metal ion, prokaryotes have evolved proteins belonging to two distinct sub-families of the ferritin family: the bacterioferritins (BFRs) and the bacterial ferritins (Ftns). Recently, Ftn homologues have also been identified and characterised in archaeon species. All of these prokaryotic ferritins function by solubilising and storing large amounts of iron in the form of a safe but bio-available mineral.
Scope of review:
The mechanism(s) by which the iron mineral is formed by these proteins is the subject of much current interest. Here we review the available information on these proteins, with particular emphasis on significant advances resulting from recent structural, spectroscopic and kinetic studies.
Current understanding indicates that at least two distinct mechanisms are in operation in prokaryotic ferritins. In one, the ferroxidase centre acts as a true catalytic centre in driving Fe2+ oxidation in the cavity; in the other, the centre acts as a gated iron pore by oxidising Fe2+ and transferring the resulting Fe3+ into the central cavity.
The prokaryotic ferritins exhibit a wide variation in mechanisms of iron core mineralisation. The basis of these differences lies, at least in part, in structural differences at and around the catalytic centre. However, it appears that more subtle differences must also be important in controlling the iron chemistry of these remarkable proteins.