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Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.
Aims
To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.
Method
Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.
Results
Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).
Conclusions
These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.
A general procedure is provided for comparing correlation coefficients between optimal linear composites. The procedure allows computationally efficient significance tests on independent or dependent multiple correlations, partial correlations, and canonical correlations, with or without the assumption of multivariate normality. Evidence from some Monte Carlo studies on the effectiveness of the methods is also provided.
The multivariate asymptotic distribution of sequential Chi-square test statistics is investigated. It is shown that: (a) when sequential Chi-square statistics are calculated for nested models on the same data, the statistics have an asymptotic intercorrelation which may be expressed in closed form, and which is, in many cases, quite high; and (b) sequential Chi-square difference tests are asymptotically independent. Some Monte Carlo evidence on the applicability of the theory is provided.
IN early August 1320, in a meeting of the Scottish parliament, a group of nobles was condemned for conspiring against their king, Robert Bruce. According to a near-contemporary chronicle, their actions were judged to be lese majesty, ‘the crime which surpasses all other crimes,’ plotting the death or downfall of one's own king. By conspiring against King Robert, these nobles had committed high treason and now faced the full penalty of the horrific death reserved for traitors. However, 14 years earlier in the late summer of 1306 it had been Bruce who was denounced as a traitor. Robert's seizure of the Scottish throne and the killing of his rival, John Comyn, which preceded it, were widely condemned as unforgiveable betrayals of both earthly laws and moral precepts. ‘The guilt of homicide and the stain of treason’ justified the brutal treatment of Bruce's family and followers by Edward I of England, a fate which Robert himself would have shared had he been captured. The wars over Scotland between 1296 and 1357 were struggles to claim and exercise authority over the kingdom. Charges of treason provided a way of signalling the illegitimacy of resistance to a ruler, stigmatising opposition, and providing the means to dispossess and eliminate those who acted against their royal lord. Their effectiveness was bound up with prevailing political conditions as much as fixed legal principles. Once he had secured control of the kingdom, the man accused of treason could bring the same charge against his own opponents. Moreover, from the late thirteenth century, treason law developed as a way of framing sovereignty. It defined the scope of royal authority by criminalising those accused of harming it within the territory and legal framework of the realm. In a struggle which centred on the status of Scotland and its rulers, treason was a central issue and a legal weapon.
If treason represented an element in the struggle to control Scotland, over a longer period and more widely it was a measure of relations between rulers and subjects and the right of the latter to resist their prince. In Scottish historiography there is an ongoing debate about the nature of this relationship during the fourteenth and fifteenth centuries.
Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.
Aims
To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.
Method
Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.
Results
Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).
Conclusions
The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.
The Brownian bridge or Lévy–Ciesielski construction of Brownian paths almost surely converges uniformly to the true Brownian path. We focus on the uniform error. In particular, we show constructively that at level N, at which there are $d=2^N$ points evaluated on the Brownian path, the uniform error and its square, and the uniform error of geometric Brownian motion, have upper bounds of order $\mathcal {O}(\sqrt {\ln d/d})$, matching the known orders. We apply the results to an option pricing example.
IT has been the prevailing view of late medieval Scotland that the political life of the realm was dominated by the relationship between its kings and the great nobles. Though bishops like James Kennedy and William Elphinstone have elbowed their way into the limelight, recognition of the roles and concerns of a wider political class has been rather limited. This applies to a landowning class of lesser nobles and freeholders, whose descendants in the sixteenth century have received much greater attention as agents of religious and social change, but who before 1500 have barely been defined as a group, let alone studied. This relative neglect also applies to the leading inhabitants of Scotland's burghs. The urban centres of the kingdom have been studied in terms of their economic activities, their social structures and their religious patronage. However, as elements in the political life of fifteenth-century Scotland, the role of burgesses and of burgh communities has tended to be treated as marginal and secondary to the relations between kings and magnates. On one level this is hardly surprising. The burghs of Scotland, small and economically unspecialised, were a far cry from the great communes of the Low Countries whose resources and ambitions made them challenging subjects for the Valois dukes of Burgundy. Nor can their political role be considered on a par with the bonnes villes de France whose support for the French monarchy was of major significance during the fifteenth century. However, the fairly recent interest in the provincial cities and boroughs of late medieval England has included a renewed sense of the political importance of urban communities, especially in relation to warfare and periods of crisis. In particular, Eliza Hartrich has directly addressed the political significance of towns and cities in fifteenth-century England. Hartrich criticised views of urban and political historians which have presented English boroughs as isolated, neutral and irrelevant in terms of national politics. She argued, instead, that boroughs and their inhabitants were a crucial component of England's political life. Their special status as legally-defined communities, their significance as settings, the interests and connections of their prominent inhabitants and their common concerns and interests as an urban sector all played an important part in wider frameworks and events.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
$270 \,\mathrm{deg}^2$
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
$\mu\mathrm{Jy\ beam}^{-1}$
rms at a spatial resolution of
$\sim$
11–18 arcsec, resulting in a catalogue of
$\sim$
220 000 sources, of which
$\sim$
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
ABSTRACT IMPACT: Racial differences in the prevalence of hypertension and endothelial (dys)function are well established, yet research investigating the mechanism(s) underlying this disparity is still lacking. OBJECTIVES/GOALS: Investigate the influence of race and the effect of serum collected from hypertensive donors on Protein Phosphatase 2A (PP2A) and endothelial nitric oxide synthase (eNOS) expression and activity in human umbilical vein endothelial cells (HUVECs) from Caucasian (CA) and African American (AA) donors. METHODS/STUDY POPULATION: HUVECs from 3 CA & 3 AA donors were cultured in parallel. Experiments were conducted between passages 5-7. At ?90% confluency, cells were serum starved ˜12hrs prior to incubating for 24 or 48 hours in one of the following conditions: 1) Control (Fetal Bovine Serum), 2) serum from normotensives (NT; 5 CA & 5 AA donors), or 3) serum from hypertensives (HT; 5 CA & 5 AA donors). NT and HT serum was pooled from donors with the following characteristics: Male, 30-50 years, nonsmokers, no comorbidities, and non-obese (BMI < 30 kg/m2). Western blotting was used to measure protein expression of total eNOS, p-eNOSS1177, total PP2A, and p-PP2AY307. For activity p-eNOSS1177/total eNOS and p-PP2AY307/ total PP2A ratio was used. A two-way ANOVA was used for statistical analysis. RESULTS/ANTICIPATED RESULTS: Irrespective of the donors’ race, there was no influence of serum treatment or interaction effect in any of the measured proteins of interest. Moreover, compared to CA, HUVECs from AA had lower expression of eNOS irrespective of condition (race p=0.01). Compared to CA, HUVECs from AA tended to have lower expression of p-eNOSS1177 irrespective of condition (race p=0.07). However, there was no racial differences in eNOS activity (p=0.68). There was no racial difference in the expression of PP2A (p=0.35), p-PP2AY307 (p=0.30), or PP2A activity (p=0.97) in all conditions. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our preliminary results suggest no influence serum constituents from hypertensive donors or race on PP2A or eNOS expression and activity in HUVECS. Future research should consider conducting proteomics profiling to compare NT and HT serum.
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.
The partial skull of a lion from Natodomeri, northwest Kenya is described. The Natodomeri sites are correlated with Member I of the Kibish Formation, dated to between 195 ka and ca. 205 ka. The skull is remarkable for its very great size, equivalent to the largest cave lions (Panthera spelaea [Goldfuss, 1810]) of Pleistocene Eurasia and much larger than any previously known lion from Africa, living or fossil. We hypothesize that this individual represents a previously unknown population or subspecies of lion present in the late Middle and Late Pleistocene of eastern Africa rather than being an indication of climate-driven size increase in lions of that time. This raises questions regarding the extent of our understanding of the pattern and causes of lion evolution in the Late Pleistocene.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
To examine variation in antibiotic coverage and detection of resistant pathogens in community-onset pneumonia.
DESIGN
Cross-sectional study.
SETTING
A total of 128 hospitals in the Veterans Affairs health system.
PARTICIPANTS
Hospitalizations with a principal diagnosis of pneumonia from 2009 through 2010.
METHODS
We examined proportions of hospitalizations with empiric antibiotic coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAER) and with initial detection in blood or respiratory cultures. We compared lowest- versus highest-decile hospitals, and we estimated adjusted probabilities (AP) for patient- and hospital-level factors predicting coverage and detection using hierarchical regression modeling.
RESULTS
Among 38,473 hospitalizations, empiric coverage varied widely across hospitals (MRSA lowest vs highest, 8.2% vs 42.0%; PAER lowest vs highest, 13.9% vs 44.4%). Detection rates also varied (MRSA lowest vs highest, 0.5% vs 3.6%; PAER lowest vs highest, 0.6% vs 3.7%). Whereas coverage was greatest among patients with recent hospitalizations (AP for anti-MRSA, 54%; AP for anti-PAER, 59%) and long-term care (AP for anti-MRSA, 60%; AP for anti-PAER, 66%), detection was greatest in patients with a previous history of a positive culture (AP for MRSA, 7.9%; AP for PAER, 11.9%) and in hospitals with a high prevalence of the organism in pneumonia (AP for MRSA, 3.9%; AP for PAER, 3.2%). Low hospital complexity and rural setting were strong negative predictors of coverage but not of detection.
CONCLUSIONS
Hospitals demonstrated widespread variation in both coverage and detection of MRSA and PAER, but probability of coverage correlated poorly with probability of detection. Factors associated with empiric coverage (eg, healthcare exposure) were different from those associated with detection (eg, microbiology history). Providing microbiology data during empiric antibiotic decision making could better align coverage to risk for resistant pathogens and could promote more judicious use of broad-spectrum antibiotics.
St Andrews was of tremendous significance in medieval Scotland. Its importance remains readily apparent in the buildings which cluster the rocky promontory jutting out into the North Sea: the towers and walls of cathedral, castle and university provide reminders of the status and wealth of the city in the Middle Ages. As a centre of earthly and spiritual government, as the place of veneration forScotland's patron saint and as an ancient seat of learning, St Andrews was the ecclesiastical capital of Scotland. This volume provides the first full study of this special and multi-faceted centre throughout its golden age. The fourteen chapters use St Andrews as a focus for the discussion of multiple aspects of medieval life in Scotland. They examine church, spirituality, urban society andlearning in a specific context from the seventh to the sixteenth century, allowing for the consideration of St Andrews alongside other great religious and political centres of medieval Europe.
Michael Brown is Professor of Medieval Scottish History, University of St Andrews; Katie Stevenson is Keeper of Scottish History and Archaeology, National Museums Scotland and Senior Lecturer in Late Medieval History, University of St Andrews.
Contributors: Michael Brown, Ian Campbell, David Ditchburn, Elizabeth Ewan, Richard Fawcett, Derek Hall, Matthew Hammond, Julian Luxford, Roger Mason, Norman Reid, Bess Rhodes, Catherine Smith, Katie Stevenson, Simon Taylor, Tom Turpie.